linoleic-acid and Body-Weight

Linoleic acid (LA) and alpha-linolenic acid (ALA) are essential fatty acids found in variable quantities in ruminant feedstuffs. Revision of French feed unit systems in 2018 has proposed the reassessment of energy requirements through a between-experiment approach expressing metabolisable energy supply as a function of the energy expenditures for maintenance and production, with these expenditures that reflect homeorhetic regulations. Based on the same approach, LA and ALA intake can be related to animal characteristics (i.e., BW) reflecting maintenance expenditures and secretion characteristics (i.e., milk yield, milk fat content and contents of LA and ALA in milk fat). Therefore, the objective of this work was to analyse the between-experiment relationships between ingested, duodenal, or absorbed flows of LA and ALA, BW and milk LA and ALA secretion by meta-analysis in mid-lactation dairy cows. These relationships were analysed using LA and ALA subsets of 96 and 99 experiments, respectively. Between-experiment regressions of daily flows of ingested, duodenal or absorbed LA and ALA on BW and milk LA and ALA flows were studied, with statistical unit defined as the mean of within-experiment treatments. For LA, the BW-associated coefficient was 0.019 (±0.0034) g absorbed LA/d per kg BW and milk LA secretion-associated coefficient was 0.70 (±0.081) g absorbed LA/g of LA secreted into milk. For ALA, the BW-associated coefficient was 0.0058 (±0.00093) g absorbed ALA/d per kg BW and milk ALA secretion-associated coefficient was 0.57 (±0.097) g absorbed ALA/g of ALA secreted into milk. When coding the diets as either control or milk fat depression diets, the BW-associated coefficient for LA was 0.017 (±0.0032) g absorbed LA/d per kg BW for both diets. For milk fat depression diets, milk LA secretion-associated coefficient was 1.02 (±0.119) g absorbed LA/g of LA secreted into milk, whereas it was 0.70 (±0.075) g absorbed LA/g of LA secreted into milk for control diets. Significant BW and milk performance coefficients were obtained in all LA and ALA equations, allowing the calculation of ingested and intestinal flows of LA and ALA based on measured BW, milk fat yield and milk fat content of LA and ALA. The relationships between ingested and intestinal flows of LA and ALA, BW and milk performance obtained in the present work could be integrated into renewed feed unit systems for energy and protein in dairy cows.

Topics: alpha-Linolenic Acid; Animal Feed; Animals; Body Weight; Cattle; Diet; Dietary Supplements; Fatty Acids; Female; Lactation; Linoleic Acid; Milk

Obesity is considered a serious global health issue. Patients have been predisposed to comorbidities such as dyslipidemia, cardiovascular diseases, diabetes, cancers, and osteoarthritis. Certain fats in the diet have been linked with an increase in obesity, such as saturated and trans-fats. Meanwhile, some dietary fats such as conjugated linoleic acids (CLAs) and medium-chain triglycerides (MCTs) could potentially reduce energy intake. Various mechanisms for reducing weight by CLAs and MCTs, such as increased lipolysis, improved intestinal microbiota, up-regulating peroxisome proliferator-activated receptors (PPARs), increased the expression of uncoupling protein of respiratory chain-1 (UCP-1), and affected satiety hormones are included. These bioactive compounds, CLAs and MCTs, should be used in moderate concentrations to prevent harmful effects such as insulin resistance for CLAs and hypercholesterolemia for MCTs. However, several studies have proposed CLAs or MCTs as adjuvants to the protocol used to minimize bodyweight. Our objective is to summarize the different causes of obesity and to discuss the effects of CLAs or MCTs on body weight and fat deposition in obese animals or humans.

Topics: Animals; Body Weight; Diet; Dietary Fats; Disease Management; Humans; Linoleic Acid; Obesity; Obesity Management; Triglycerides

Studies in mice have indicated that feeding diets containing 0.5-1% conjugated linoleic acid (CLA) considerably reduces body fat. These findings have attracted much interest because of the potential use of CLA as a tool to promote weight loss in humans. Several CLA studies in humans have now been published, and the objective of the present review was to give an overview of these experiments. Most of the studies were done in free-living subjects and were not strictly controlled for nutrient and energy intakes. None of the studies found a significant reduction in body weight, and only 2 studies showed a significant but relatively small body fat-lowering effect. Some studies suggested that CLA may have a tendency to increase lean body mass. Furthermore, there are indications from animal studies that CLA may have effects on plasma lipids. However, only one study in humans showed a significant HDL-cholesterol-lowering effect of CLA; in all the other studies, there were no significant effects on plasma total, LDL-, and HDL-cholesterol concentrations or on plasma triacylglycerol concentrations. Thus, the results of the studies in humans indicate that the effect of CLA on body fat is considerably less than that anticipated from mice studies and that CLA has no major effect on plasma lipids.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Composition; Body Weight; Energy Metabolism; Humans; Insulin; Leptin; Linoleic Acid; Lipids; Meta-Analysis as Topic

Isomers of conjugated linoleic acid (CLA) are found in beef, lamb and dairy products. Diets containing CLA reduce adipose mass in various depots of experimental animals. In addition, CLA delays the onset of diabetes in the ZDF rat model for obesity-linked type 2 diabetes mellitus. We hypothesize that there would be an inverse association of CLA with body weight and serum leptin in subjects with type 2 diabetes mellitus. In this double-blind study, subjects with type 2 diabetes mellitus were randomized into one of two groups receiving either a supplement containing mixed CLA isomers (CLA-mix; 8.0 g daily, 76% pure CLA; n = 12) or a supplement containing safflower oil (placebo; 8.0 g daily safflower oil, n = 9) for 8 wk. The isomers of CLA in the CLA-mix supplement were primarily c9t11-CLA ( approximately 37%) and t10c12-CLA ( approximately 39%) in free fatty acid form. Plasma levels of CLA were inversely associated with body weight (P < 0.05) and serum leptin levels (P < 0.05). When levels of plasma t10c12-CLA isomer were correlated with changes in body weight or serum leptin, t10c12-CLA, but not c9t11-CLA, was inversely associated with body weights (P < 0.05) and serum leptin (P < 0.02). These findings strongly suggest that the t10c12-CLA isomer may be the bioactive isomer of CLA to influence the body weight changes observed in subjects with type 2 diabetes. Future studies are needed to determine a causal relationship, if any, of t10c12-CLA or c9t11-CLA to modulate body weight and composition in subjects with type 2 diabetes. Furthermore, determining the ability of CLA isomers to influence glucose and lipid metabolism as well as markers of insulin sensitivity is imperative to understanding the role of CLA to aid in the management of type 2 diabetes and other related conditions of insulin resistance.

Topics: Adult; Animals; Body Weight; Diabetes Mellitus, Type 2; Humans; Leptin; Linoleic Acid; Obesity; Randomized Controlled Trials as Topic

CLA comprises a group of unsaturated FA isomers with a variety of biological effects in experimental animals. CLA reduces body fat accumulation in animal models and has been suggested to have significant effects on lipid and glucose metabolism, e.g., antidiabetic effects in obese Zucker rats. It has been proposed that the trans10-cis12 isomer is the active isomer associated with the antiobesity and insulin-sensitizing properties of CLA. The metabolic effects in humans in general, and isomer-specific effects specifically, are not well characterized. In a series of controlled studies in humans, we investigated the effects of CLA (given as the commercially available mixture of isomers and as the purified trans10-cis12 CLA isomer) on anthropometry, lipid and glucose metabolism, and markers of lipid peroxidation. Preliminary results indicate that CLA may slightly decrease body fat in humans also, particularly abdominal fat, but there is no effect on body weight or body mass index. There is no simultaneous improvement in lipid or glucose metabolism. Rather, the trans10-cis12 CLA isomer unexpectedly caused significant impairment of the peripheral insulin sensitivity as well as of blood glucose and serum lipid levels. In addition, CLA markedly elevated lipid peroxidation. Thus, the metabolic effects of CLA in humans seem complex; further studies, especially of isomer-specific effects and for longer time periods, are warranted.

Topics: Body Weight; Dietary Supplements; Fatty Acids, Unsaturated; Humans; Linoleic Acid

Conjugated linoleic acid has been shown to reduce body fat accumulation in several animal models. We have conducted several studies in AKR/J mice showing that CLA reduces body fat accumulation whether animals are fed a high-fat or low-fat diet, with no effect on food intake. One mechanism by which CLA reduces body fat is by increased energy expenditure, which is observed within one week of CLA feeding and is sustained for at least six weeks. The increased energy expenditure is sufficient to account for the decreased fat accumulation. Increased uncoupling protein gene expression does not appear to be involved in the increased energy expenditure. We have observed increased fat oxidation but no decrease in de novo fat biosynthesis with CLA feeding. We have also observed increased liver weights and plasma insulin levels with higher doses of CLA. In all of the studies we have conducted to date we have used a CLA preparation that contains several isomers, primarily c9,t11 and t10,c12. It was assumed that the active form was c9,t11, as CLA was identified as an anticarcinogenic compound from cooked beef, of which the c9,t11 form accounts for 60% to 80% of the CLA. Most of the studies conducted so far must be repeated using the purified isomers in order to determine which isomers are responsible for each of the identified actions of CLA.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Dietary Fats, Unsaturated; Dose-Response Relationship, Drug; Energy Metabolism; Linoleic Acid; Male; Mice; Mice, Inbred AKR; Oxidation-Reduction; Time Factors

Increasing dietary fat content increases mammary gland tumorigenesis in laboratory rodents. The effect can be attributed only in part to increasing energy intake, which itself increases tumorigenesis. Restriction of dietary or energy intake, sufficient to reduce body weight, reduces mammary gland tumorigenesis. Consideration of these effects has led to discussion of the possible need for changes in the feeding of laboratory rodents in carcinogenesis bioassays and other chronic studies. Studies of endocrine or other growth factors for the mammary gland have not identified specific effects of dietary fat or energy. In addition, tumorigenesis in other organs responds similarly to increased fat or decreased energy intake, indicating that the mechanisms are not, or not entirely, specific for the mammary gland. Extrapolations of results between species must always be made with caution, but the marked effects of dietary fat and energy in rodent tumorigenesis models must be considered in designing diet advice for humans.

Topics: Animals; Body Weight; Diet; Dietary Fats; Energy Intake; Female; Humans; Linoleic Acid; Linoleic Acids; Mammary Neoplasms, Experimental; Rats

Topics: Blood Pressure; Body Weight; Dietary Fats; Fatty Acids; Kidney; Linoleic Acid; Linoleic Acids; Lipid Metabolism; Muscle, Smooth, Vascular; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Sodium Chloride; Sympathetic Nervous System

The objective of this study was to investigate the effects of dietary linoleic acid level and the ratio of linoleic acid:linolenic acid (LA:ALA) on the growth performance, expression of genes associated with lipid metabolism, and inflammatory status of grow-finish pigs. A total of 300 growing pigs (body weight [BW] = 41.1 ± 6.3 kg) were randomly assigned to either a high (30 g/kg; HLA) or low (15 g/kg; LLA) dietary linoleic acid level with a high (23:1; HR), moderate (13:1; MR) or low (4:1; LR) dietary LA:ALA in a 2 × 3 factorial design. Diets were fed across three 28-d phases and were balanced for dietary metabolizable energy. Pigs were housed five pigs per pen in single-sex pens. Blood samples were collected on days 0, 21, 42, and 84, and synovial fluid was collected from the hock joint on days 0 and 84 for inflammatory marker analysis. Data were analyzed as repeated measures using PROC MIXED (SAS 9.4) with initial BW as a covariate, pen as the experimental unit, and LA level, LA:ALA, sex, phases, and their interactions as fixed effects. Compared to HLA, LLA pigs tended to have increased BW at days 56 and 84 (P = 0.088). There was no effect of LA × LA:ALA for growth performance. For the overall days 0 to 84 growth period, pigs fed HR had increased ADG compared to MR, with pigs receiving LR performing intermediate of MR and HR. Gilts receiving HR diets had increased day 84 BW compared to gilts receiving the low and moderate LA:ALA (P = 0.006), which was a result of improved overall days 0 to 84 ADG compared to gilts receiving the MR diets (P = 0.023). Barrows fed LR had improved BW on day 56 compared to MR and HR and higher final BW compared to HR, with MR performing intermediately (P = 0.006). This was a result of greater days 0 to 84 ADG (P = 0.023). Overall, C-reactive protein (CRP), tumor necrosis factor-α (TNFα), and interleukin-6 were reduced in the plasma of pigs over time (P ≤ 0.037). Across all treatments, CRP and TNFα were reduced in the hock and carpus synovial fluid on day 84 vs. day 0 (P ≤ 0.049). In conclusion, LA:ALA ratios utilized in this study can be fed at varying linoleic acid levels without impacting growth or inflammation. Additionally, LA:ALA ratios can differentially impact the growth of gilts and barrows.. Previous research in lactating sows has reported that dietary inclusion of the essential fatty acids linoleic acid and linolenic acid is important for performance. Research in grow–finish pigs has shown an improvement in gilt growth performance when fed differing linoleic:linolenic acid ratios (LA:ALA); however, further research evaluating LA:ALA in diets with similar metabolizable energy is needed in growing pigs. In the present research, a 23:1 dietary essential fatty acid ratio increased the final body weight of gilts compared to a 13:1 or 4:1 LA:ALA, while barrows fed a 4:1 dietary essential fatty acid ratio had increased gain and final body weight compared to a 23:1 LA:ALA. Plasma and synovial fluid inflammatory markers were also reduced with time and were unaffected by dietary LA:ALA or linoleic acid inclusion. Dietary essential fatty acid ratio can differentially impact the growth of barrows and gilts, with no impact on systemic or joint inflammation.

Topics: Animal Feed; Animals; Body Composition; Body Weight; Diet; Fatty Acids; Female; Linoleic Acid; Sus scrofa; Swine; Tumor Necrosis Factor-alpha; Weight Gain

The objective of this trial was to investigate the effects of feeding a soybean oil refining by-product (SORB), made up mainly of sodium salts of long-chain fatty acids, on reproductive performance and productivity of 36 early lactation Holstein cows managed in a free-stall barn or on annual rye-ryegrass pasture. In this 2 x 2 factorial arrangement of treatments, cows consumed 0 or 0.5 kg/d of SORB as part of a total mixed ration for barn cows or as part of a grain supplement fed to cows on intensively, rotationally stocked pasture. Blood was sampled 3 times weekly and plasma was measured for progesterone to assess ovarian activity. Estrus activity was recorded using the HeatWatch estrus detection system. Although average 14-wk milk production (37.2 kg/d) was not different among treatments, barn cows had more persistent lactations than did grazing cows. Cows housed in the barn lost less body weight and returned to initial body weight sooner and had lower mean concentrations of plasma nonesterified fatty acids (464 vs. 261 mEq/L) than those managed on pasture. The milk fat of cows on pasture contained greater proportions of conjugated linoleic acid and linolenic acid but a corresponding 0.22 percentage unit decrease in milk fat concentration (3.39 vs. 3.16%). Cows managed on pasture had greater peak concentrations of plasma progesterone during the first estrous cycle. Cows managed on pasture and fed SORB had the greatest accumulation of plasma progesterone over the 14 wk of the study (SORB x housing interaction). These cows experienced the most mounts during their first estrus (9.3) and pregnancy rate was also greatest for this treatment (62.5%). Feeding SORB did not affect production of milk, fat, or protein. Loss of body condition was less in cows fed SORB. Ruminal fluid concentration of propionate increased and ruminal pH decreased in cows fed SORB. A lower proportion of fatty acids less than 18 carbons in length was found in the milk fat of cows fed SORB, thus indicating lower de novo synthesis of fatty acids. Higher proportions of C18:2n-6 and conjugated C18:2 were found in the milk fat of cows fed SORB. Based on concentrations of plasma progesterone, cows fed SORB experienced their first ovulation earlier (26.7 vs. 42.4 d postpartum) than did cows not supplemented with SORB. Neither housing system nor SORB supplementation influenced detection of first estrus (50.5 d) or the mean length of each estrus period (447 min).

Topics: alpha-Linolenic Acid; Animals; Body Composition; Body Weight; Cattle; Diet; Dietary Fats; Edible Grain; Estrus; Estrus Detection; Fats; Fatty Acids, Volatile; Female; Hydrogen-Ion Concentration; Lactation; Linoleic Acid; Milk; Milk Proteins; Pregnancy; Progesterone; Propionates; Reproduction; Rumen; Soybean Oil

Alpha-linolenic acid [ALA, 18:3(n-3)] and linoleic acid [LA, 18:2(n-6)] have comparable effects on serum lipid and lipoprotein concentrations, but their effects on lipoprotein subclass distributions and particle sizes are unknown. It is also not known whether these effects are changed by the ALA:LA ratio in the diet. To address these questions, healthy subjects (n = 54) consumed a control diet providing 7% of energy (En%) as LA and 0.4 En% as ALA during a 4-wk run-in period. For the following 6 wk of intervention, each diet was consumed by 18 subjects: the control diet, a low-LA diet (3 En% LA, 0.4 En% ALA), or a high-ALA diet (7 En% LA, 1.1 En% ALA). The ALA:LA ratio for the control diet was 1:19 and was 1:7 for the other 2 diets. Compared with the control group, LDL cholesterol decreased significantly in the ALA group (-0.32 mmol/L, P = 0.024), as did total cholesterol, apolipoprotein (apo) B, and the total:HDL cholesterol ratio. None of the dietary interventions affected HDL cholesterol, apo A-1, or triacylglycerol concentrations. The decrease in total VLDL particle concentrations in the low-LA group was due mainly to a decrease in medium VLDL (-16 nmol/L, P = 0.018) and in the high-ALA group to a decrease in small VLDL (-14 nmol/L, P = 0.044). We conclude that the ALA:LA ratio does not affect the serum lipoprotein profile. Compared with the control and LA diets, ALA lowered LDL cholesterol concentrations, possibly caused by the decrease in small VLDL.

Topics: alpha-Linolenic Acid; Body Weight; Dietary Supplements; Double-Blind Method; Energy Metabolism; Humans; Linoleic Acid; Lipids; Lipoproteins; Lipoproteins, LDL; Lipoproteins, VLDL; Patient Compliance; Phospholipids

Isomers of conjugated linoleic acid (CLA) are found in beef, lamb and dairy products. Diets containing CLA reduce adipose mass in various depots of experimental animals. In addition, CLA delays the onset of diabetes in the ZDF rat model for obesity-linked type 2 diabetes mellitus. We hypothesize that there would be an inverse association of CLA with body weight and serum leptin in subjects with type 2 diabetes mellitus. In this double-blind study, subjects with type 2 diabetes mellitus were randomized into one of two groups receiving either a supplement containing mixed CLA isomers (CLA-mix; 8.0 g daily, 76% pure CLA; n = 12) or a supplement containing safflower oil (placebo; 8.0 g daily safflower oil, n = 9) for 8 wk. The isomers of CLA in the CLA-mix supplement were primarily c9t11-CLA ( approximately 37%) and t10c12-CLA ( approximately 39%) in free fatty acid form. Plasma levels of CLA were inversely associated with body weight (P < 0.05) and serum leptin levels (P < 0.05). When levels of plasma t10c12-CLA isomer were correlated with changes in body weight or serum leptin, t10c12-CLA, but not c9t11-CLA, was inversely associated with body weights (P < 0.05) and serum leptin (P < 0.02). These findings strongly suggest that the t10c12-CLA isomer may be the bioactive isomer of CLA to influence the body weight changes observed in subjects with type 2 diabetes. Future studies are needed to determine a causal relationship, if any, of t10c12-CLA or c9t11-CLA to modulate body weight and composition in subjects with type 2 diabetes. Furthermore, determining the ability of CLA isomers to influence glucose and lipid metabolism as well as markers of insulin sensitivity is imperative to understanding the role of CLA to aid in the management of type 2 diabetes and other related conditions of insulin resistance.

Topics: Adult; Animals; Body Weight; Diabetes Mellitus, Type 2; Humans; Leptin; Linoleic Acid; Obesity; Randomized Controlled Trials as Topic

Supplementation with conjugated linoleic acid (CLA) induces a number of physiological effects in experimental animals, including reduced body fat content, decreased aortic lipid deposition, and improved serum lipid profile. Controlled trials on the effects of CLA in humans have hitherto been scarce. The aim of this study was to evaluate the effects of supplementation with CLA in healthy humans on anthropometric and metabolic variables and on the fatty acid composition of serum lipids and thrombocytes. Fifty-three healthy men and women, aged 23-63 yr, were randomly assigned to supplementation with CLA (4.2 g/d) or the same amount of olive oil during 12 wk in a double-blind fashion. The proportion of body fat decreased (-3.8%, P< 0.001) in the CLA-treated group, with a significant difference from the control group (P = 0.050). Body weight, body mass index, and sagittal abdominal diameter were unchanged. There were no major differences between the groups in serum lipoproteins, nonesterified fatty acids, plasma insulin, blood glucose, or plasminogen activator inhibitor 1 (PAI-1). In the CLA group the proportions of stearic, docosatetraenoic, and docosapentaenoic acids increased in serum lipids and thrombocytes, while proportions of palmitic, oleic, and dihomo-gamma-linolenic acids decreased, causing a decrease of the estimated delta-6 and delta-9 and an increase in the delta-5 desaturase activities. These results suggest that supplementation with CLA may reduce the proportion of body fat in humans and that CLA affects fatty acid metabolism. No effects on body weight, serum lipids, glucose metabolism, or PAI-1 were seen.

Topics: Adult; Anthropometry; Apolipoproteins; Blood Glucose; Blood Platelets; Body Composition; Body Weight; Dietary Supplements; Double-Blind Method; Fatty Acids; Female; Humans; Linoleic Acid; Lipid Metabolism; Lipid Peroxidation; Lipids; Male; Middle Aged

Patients with cystic fibrosis who have steatorrhea frequently are underweight and have essential fatty acid (EFA) depletion, which is associated with a poor clinical course. It has been stated that poor EFA status is difficult to correct in patients with cystic fibrosis, and an impaired EFA metabolism with reduced synthesis of long-chain polyunsaturated fatty acids has been proposed. In this study, the effects of an oral energy supplement rich in linoleic acid were investigated in patients with cystic fibrosis who had a body weight below 95% of normal for height.. Thirty-six patients (16 girls) more than 4 years of age were randomized either to a control group (n = 20, age 13.3 +/- 3.8 years, mean +/- SD) receiving intensive dietary counseling only, or an intervention group (n = 16, age, 10.4 +/- 4.3 years) treated for 3 months with dietary counseling plus 628 +/- 254 mL (= kcal) per day of an energy supplement rich in fat (31% of energy) and linoleic acid (16% of energy).. In contrast to the control group, the patients with supplemented diets achieved significant increases of energy intake (2189 +/- 731 kcal/day vs. 2733 +/- 762 kcal/day), weight for height (82.8% +/- 8.6% vs. 84.8% +/- 9.6% of normal), and body fat (5.1 +/- 1.7 kg vs. 5.8 +/- 2.2 kg) as well as the initially low values of plasma phospholipid linoleic acid (11.8% +/- 1.1% vs. 17.6% +/- 1.6% of total phospholipid fatty acids) and its main metabolite arachidonic acid (4.4% +/- 0.4% vs. 5.9% +/- 0.3%).. Patients with cystic fibrosis with low body weight and poor EFA status benefit from EFA-rich energy supplements and can synthesize arachidonic acid from the precursor linoleic acid.

Topics: Adolescent; Body Weight; Celiac Disease; Child; Cystic Fibrosis; Dietary Supplements; Energy Intake; Fatty Acids, Essential; Female; Humans; Linoleic Acid; Male

This multicenter, parallel group study determined plasma phospholipid and red blood cell (RBC) phosphatidylcholine and phosphatidylethanolamine fatty acids, plasma cholesterol, apo A-1 and B, growth and visual acuity (using the acuity card procedure) in term infants fed from birth to 90 d of age with formula containing palm-olein, high oleic sunflower, coconut and soy oil (22.2% 16:0, 36.2% 18:1, 18% 18:2n-6, 1.9% 18:3n-3) (n = 59) or coconut and soy oil (10.3% 16:0 18:6% 18:1, 34.2% 18:2n-6, 4.7% 18:3n-3) (n = 57) or breast-fed (n = 56) with no formula supplementation. Different centers in North America were included to overcome potential bias due to differences in n-6 or n-3 fatty acids at birth or in breast-fed infants that might occur in a single-site study. Plasma and RBC phospholipid docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), cholesterol and apo B were significantly lower in the formula- than breast-fed infants. There were no differences in looking acuity or growth among the breast-fed and formula-fed infants. No significant relations were found between DHA and looking acuity, or AA and growth within or among any of the infant groups. This study provides no evidence to suggest the formula provided inadequate n-6 or n-3 fatty acids for growth and looking acuity for the first 3 mon after birth.

Topics: alpha-Linolenic Acid; Apolipoproteins; Arachidonic Acid; Body Weight; Cholesterol; Docosahexaenoic Acids; Erythrocytes; Fatty Acids; Humans; Infant Food; Infant Nutritional Physiological Phenomena; Infant, Newborn; Linoleic Acid; Linoleic Acids; Lipids; Milk, Human; Phospholipids; Triglycerides; Visual Acuity

To determine the effect of alpha-linolenic acid (ALA) intake (or the dietary linoleic acid [LA]/ALA ratio) on the growth and visual function of term infants.. Normal term infants were assigned randomly and in masked fashion at birth to receive formulas with approximately 16% of total fatty acids as LA and 0.4%, 1.0%, 1.7%, or 3.2% of fatty acids as ALA (LA/ALA ratios of 44, 18.2, 9.7, and 4.8) for the first 4 months of life. The fatty acid pattern of plasma phospholipids was determined shortly after birth and at approximately 21, 60, and 120 days of age. Anthropometric data were obtained at the same times and also at approximately 240 days of age. Transient visual evoked responses (VERs) were measured at approximately 120 and 240 days of age. For comparisons, anthropometric and VER data also were obtained in infants who were exclusively breast-fed for the first 4 months of life.. Infants who received the formula with 3.2% ALA (LA/ALA ratio, 4.8) had higher plasma concentrations of phospholipid docosahexaenoic acid (DHA) but lower concentrations of arachidonic acid at 21, 60, and 120 days of age. Mean weight of this group at 120 days of age was 760 gm less (p < 0.05) than the mean weight of the group that received the formula with 0.4% ALA (LA/ALA ratio, 44). Despite differences in plasma phospholipid DHA contents among groups, neither VER latency nor amplitude differed significantly among formula groups or between any formula group and age-matched, breast-fed infants.. The highest versus the lowest ALA intake (or the lowest vs the highest LA/ALA ratio) resulted in higher plasma phospholipid DHA content from 21 to 120 days of age but was not associated with improved visual function as assessed by transient VER. Moreover, mean body weight of infants who received the highest versus lowest ALA intake was less at 120 days (p < 0.05). These data suggest that the lower LA/ALA ratios currently recommended for infant formulas should not be adopted until the effect of such ratios on growth are evaluated more completely.

Topics: alpha-Linolenic Acid; Arachidonic Acids; Body Height; Body Weight; Breast Feeding; Case-Control Studies; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Evoked Potentials, Visual; Follow-Up Studies; Gestational Age; Growth; Humans; Infant Food; Infant Nutritional Physiological Phenomena; Infant, Newborn; Linoleic Acid; Linoleic Acids; Nutrition Policy; Phospholipids; Photic Stimulation; Reaction Time; Skinfold Thickness; Vision, Ocular; Visual Cortex

Essential fatty acid deficiency as a result of inadequate linoleic acid impairs growth in healthy infants and is common in infants with malabsorption due to cystic fibrosis (CF). We investigated the effect of dietary linoleic acid intake on the growth of infants with CF. In this study, predigested formula preparations A and B, with linoleic acid contents of 12% and 7% of energy, respectively, were fed before and after 1989 to infants enrolled in the evaluation and treatment protocol of the Wisconsin CF Neonatal Screening Project. Outcome was assessed from height-for-age (HAZ) and weight-for-age (WAZ) Z scores on follow-up exams during the first year. Baseline characteristics did not differ significantly between groups A (n = 43) and B (n = 33). At diagnosis, 53% of the enrolled infants (n = 76) showed low plasma linoleic acid concentrations and 22% had a high ratio of triene to tetraene. After correcting for the effect of potentially confounding variables, we found that HAZ (by .27, P < 0.05) and WAZ (by 0.26, P = 0.081) were higher in group A than in group B. This occurred despite a significantly higher energy intake in group B. This difference was most pronounced between 6 and 9 mo of age. Our results suggest that a high linoleic acid content in formula benefits infants with CF because it optimizes nutrition, growth, and feeding efficiency.

Topics: Age Factors; Body Height; Body Weight; Cystic Fibrosis; Deficiency Diseases; Energy Intake; Fatty Acids, Essential; Female; Growth; Growth Disorders; Humans; Infant; Infant Food; Infant, Newborn; Linoleic Acid; Linoleic Acids; Longitudinal Studies; Male; Prevalence; Wisconsin

Experiments were conducted to determine: 1) whether the beneficial effects of increasing the dietary protein on egg weight during the early stages of egg production is due to a higher intake of methionine or total nitrogen and other essential amino acids; and 2) whether the beneficial effect of supplemental fat on egg weight during the early stages of egg production is due to a higher intake of linoleic acid or the presence of fat per se in the diet. Experiment 1 involved the factorial arrangements of three levels of protein (17, 19, and 21%) and three levels of methionine (.34, .38, and .42%). Experiment 2 involved a control diet with no supplemental fat or with a supplemental level of 2 or 4% of tallow, blended fat, or corn oil. Experiment 3 involved factorial arrangements of two body weight groups (light and heavy), two levels of blended fat (0 and 4%), and two levels of protein (17 and 21%). Pullets were fed the experimental diets from 18 to 38 wk of age in all of the experiments. In Experiment 3, pullets from different regimens were maintained on a 16.5% protein diet up to 62 wk of age. Egg weight responses during the early stages of egg production to increasing the protein or methionine level (Experiment 1) or supplemental sources of fats (Experiment 2) were small and only the methionine effect on egg weight was significant (P < .05). In Experiment 3, egg weight during the early stages of egg production was increased due to increasing the protein level or adding fat to the diets (P < .05). However, significant interactions were detected between protein and fat for most of the traits. Most traits were increased due to adding 4% fat to high-protein (21%) diets (P < .05), but were reduced due to adding 4% fat to low-protein (17%) diets (P < .05). Most of the beneficial effects of a high protein level or supplemental fat on early egg weight discontinued upon changing the feeds to a 16.5% protein diet. Egg weight of the heavy-weight groups remained greater than the light-weight groups for the entire experiment (P < .05).

Topics: Amino Acids, Essential; Analysis of Variance; Animal Feed; Animals; Body Weight; Chickens; Dietary Fats; Dietary Proteins; Eggs; Female; Linoleic Acid; Linoleic Acids; Methionine

We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200 micrograms/min). Thirty-eight patients were randomly assigned to increase dietary polyunsaturated:saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products (n = 18, two dropouts, analysis was performed in n = 16) or to continue their usual diet (n = 20). The total fat and protein content of the diet was unaltered. Clinical characteristics, albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7 +/- 4 to 11 +/- 2 energy % and polyunsaturated:saturated fatty acids ratio rose from 0.60 +/- 0.28 to 0.96 +/- 0.16 (p less than 0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p less than 0.02) and 55% (95% confidence interval, 11 to 127) (p less than 0.01) during the second year. Glomerular filtration rate remained unaltered and filtration fraction tended to rise (p less than 0.05 compared to usual diet group). In the usual diet group, albuminuria did not significantly increased by 16% (95% confidence interval, -17 to 38) and glomerular filtration rate declined during the second year. Blood pressure tended to rise similarly in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Albuminuria; Blood Pressure; Body Weight; Diabetes Mellitus, Type 1; Diet, Diabetic; Dietary Fats; Female; Glomerular Filtration Rate; Humans; Linoleic Acid; Linoleic Acids; Lipids; Lipoproteins; Male; Prospective Studies; Regression Analysis; Renal Circulation

Fifty-four healthy, omnivore normotensive volunteers aged 20-59 years were randomly allocated either to a control group eating a low polyunsaturated to saturated fat ratio (P/S ratio) diet (0.3) throughout, or to one of two experimental groups eating a high P/S ratio diet (1.0) for one of two 6-week experimental periods. Changes in other components were avoided. Twenty-four hour diet records showed substantial changes in the P/S ratio for experimental groups when on the high P/S ratio diet (0.3 to 1.0). There were significant increases in relative concentrations of linoleic acid in plasma phospholipids when on the high P/S ratio diet. There was no consistent effect of dietary P/S ratio elevation from 0.3 to 1.0 on group mean systolic and diastolic blood pressures. Adjustment of blood pressure changes for changes in electrolytes, other dietary components, plasma lipids, weight and other lifestyle variables did not alter this result. It was concluded that the blood pressure lowering effect of a vegetarian diet reported previously was unlikely to have been due to changes in dietary P/S ratio.

Topics: Adult; Blood Pressure; Body Weight; Clinical Trials as Topic; Diet, Vegetarian; Dietary Fats; Energy Intake; Fats, Unsaturated; Female; Humans; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Phospholipids; Random Allocation; Thromboxanes

Antibiotic residue has become an emerging environmental contaminant, while the toxicological effects and underlying mechanisms caused by the co-exposure to multiple veterinary antibiotics were rarely studied. In this study, male Sprague Dawley rats were exposed to monensin (M) (1, 2, 10 mg/(kg·body weight (BW)) combined with sulfamethazine (S) (60, 120, 600 mg/(kg·BW)) or single drugs for 28 consecutive days. The body weight, hematological and blood biochemical parameters, organ coefficients, and histopathology were analyzed to discover their combined toxicity effect. Transcriptomic analysis was used to reveal the possible mechanisms of their joint toxicity. Compared with the control group, the weight gain rate was significantly reduced in the H-M+S and H-S, and alkaline phosphatase in H-M+S was significantly increased. Furthermore, relative liver and kidneys weight was significantly increased, and the liver of H-M+S showed more severe lesions in histopathological analysis. For H-M+S, H-M and H-S, transcriptomic results showed that 344, 246, and 99 genes were differentially expressed, respectively. The Gene Ontology terms mainly differ in sterol biosynthetic process and steroid hydroxylase activity. The Kyoto Encyclopedia of Genes and Genome pathways showed abnormal retinol metabolism, metabolism of xenobiotics by cytochrome P450, and drug metabolism-cytochrome 450; the common 30 genes were screened from the network of protein-protein interaction. The results showed that mixed contamination of M and S produces hepatotoxicity by interfering with linoleic acid metabolism, retinol metabolism and CYP450 enzyme-dominated drug metabolism. Further analysis showed that Cyp1a2, Cyp2c61, Ugt1a3, and Ugt1a5 might be the key genes. These findings could provide more evidence for investigating the toxic effects and metabolism of mixed antibiotics contamination in mammals.

Topics: Alkaline Phosphatase; Animals; Anti-Bacterial Agents; Body Weight; Cytochrome P-450 CYP1A2; Cytochrome P-450 Enzyme System; Linoleic Acid; Liver; Male; Mammals; Monensin; Rats; Rats, Sprague-Dawley; Steroid Hydroxylases; Sterols; Sulfamethazine; Transcriptome; Vitamin A; Xenobiotics

The aim of the study was to evaluate the effect of different types of high-fat diets (HFDs) on the proteomic profile of mouse liver. The analysis included four dietary groups of mice fed a standard diet (STD group), a high-fat diet rich in SFAs (SFA group), and high-fat diets dominated by PUFAs with linoleic acid (LA, C18:2n-6) to α-linolenic acid (ALA, C18:3n-3) ratios of 14:1 (14:1 group) and 5:1 (5:1 group). After three months of diets, liver proteins were resolved by two-dimensional gel electrophoresis (2DE) using 17 cm non-linear 3-10 pH gradient strips. Protein spots with different expression were identified by MALDI-TOF/TOF. The expression of 13 liver proteins was changed in the SFA group compared to the STD group (↓: ALB, APOA1, IVD, MAT1A, OAT and PHB; ↑: ALDH1L1, UniProtKB-Q91V76, GALK1, GPD1, HMGCS2, KHK and TKFC). Eleven proteins with altered expression were recorded in the 14:1 group compared to the SFA group (↓: ARG1, FTL1, GPD1, HGD, HMGCS2 and MAT1A; ↑: APOA1, CA3, GLO1, HDHD3 and IVD). The expression of 11 proteins was altered in the 5:1 group compared to the SFA group (↓: ATP5F1B, FTL1, GALK1, HGD, HSPA9, HSPD1, PC and TKFC; ↑: ACAT2, CA3 and GSTP1). High-PUFA diets significantly affected the expression of proteins involved in, e.g., carbohydrate metabolism, and had varying effects on plasma total cholesterol and glucose levels. The outcomes of this study revealed crucial liver proteins affected by different high-fat diets.

Topics: alpha-Linolenic Acid; Animals; Body Weight; Diet, High-Fat; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Linoleic Acid; Liver; Male; Mice; Proteome; Proteomics

Dietary intakes of linoleic acid (LA) have increased, including in women of reproductive age. Changes in maternal gut microbiome have been implicated in the metabolic adaptions that occur during pregnancy. We aimed to investigate whether consumption of a diet with elevated LA altered fecal microbiome diversity before and during pregnancy. Female Wistar-Kyoto rats consumed a high-LA diet (HLA: 6.21% of energy) or a low-LA diet (LLA: 1.44% of energy) for 10 wk before mating and during pregnancy. DNA was isolated from fecal samples before pregnancy [embryonic day 0 (E0)], or during pregnancy at E10 and E20. The microbiome composition was assessed with 16S rRNA sequencing. At E0, the beta-diversity of LLA and HLA groups differed with HLA rats having significantly lower abundance of the genera

Topics: Adult; Animals; Body Weight; Diet; Diet, High-Fat; Feces; Female; Gastrointestinal Microbiome; Humans; Linoleic Acid; Pregnancy; Rats; Rats, Inbred WKY; RNA, Ribosomal, 16S

Vegetable oils are frequently used as solvents for lipophilic materials; accordingly, the effects of their components should be considered in animal experiments. In this study, the effects of various vegetable oils on the course of Trypanosoma congolense infection were examined in mice. C57BL/6J mice were orally administered four kinds of oils (i.e., coconut oil, olive oil, high oleic safflower oil, and high linoleic safflower oil) with different fatty acid compositions and infected with T. congolense IL-3000. Oil-treated mice infected with T. congolense showed significantly higher survival rates and lower parasitemia than those of control mice. Notably, coconut oil, which mainly consists of saturated fatty acids, delayed the development of parasitemia at the early stage of infection. These results indicated that vegetable oil intake could affect T. congolense infection in mice. These findings have important practical implications; for example, they suggest the potential effectiveness of vegetable oils as a part of the regular animal diet for controlling tropical diseases and indicate that vegetable oils are not suitable solvents for studies of the efficacy of lipophilic agents against T. congolense.

Topics: Animals; Body Weight; Coconut Oil; Energy Intake; Linoleic Acid; Male; Mice; Mice, Inbred C57BL; Oleic Acid; Olive Oil; Parasitemia; Plant Oils; Safflower Oil; Trypanosoma congolense; Trypanosomiasis, African

Monk fruit extract (MFE) is a natural sweetener that has been used as an ingredient of food and pharmaceutical products. The effects of feeding synbiotic yogurt fortified with MFE to rats with type 2 diabetes induced by high-fat diet and streptozotocin on serum lipid levels and hepatic AMPK signaling pathway were evaluated. Results showed that oral administration of the synbiotic yogurt fortified with MFE could improve serum lipid levels, respiratory exchange rate, and heat level in type 2 diabetic rats. Transcriptome analysis showed that synbiotic yogurt fortified with MFE may affect the expression of genes involved in binding, catalytic activity, and transporter activity. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these differentially expressed genes were related to AMPK signaling pathway, linoleic acid metabolism, and α-linolenic acid metabolism. Western blotting confirmed that synbiotic yogurt fortified with MFE could activate AMPK signaling and improve the protein level of the hepatic gluconeogenic enzyme G6Pase in diabetic rats. The results indicated that MFE could be a novel sweetener for functional yogurt and related products.

Topics: alpha-Linolenic Acid; AMP-Activated Protein Kinases; Animals; Body Weight; Cucurbitaceae; Diabetes Mellitus, Type 2; Gene Expression Profiling; Glucose-6-Phosphatase; Intracellular Signaling Peptides and Proteins; Linoleic Acid; Lipids; Liver; Male; Phosphoenolpyruvate Carboxykinase (GTP); Plant Extracts; Rats; Respiration; Signal Transduction; Sweetening Agents; Synbiotics; Yogurt

A diet high in

Topics: Animals; Bile Acids and Salts; Body Weight; Cecum; Diet, High-Fat; Fatty Acids, Omega-6; Female; Gene Expression; Homeostasis; Linoleic Acid; Liver; Male; Mice, Inbred C57BL; Mice, Transgenic; Microfilament Proteins; RNA-Binding Proteins; Transgenes

Dietary nitrate lowers blood pressure and improves athletic performance in humans, yet data supporting observations that it may increase cerebral blood flow and improve cognitive performance are mixed. We tested the hypothesis that nitrate and nitrite treatment would improve indicators of learning and cognitive performance in a zebrafish (Danio rerio) model. We utilized targeted and untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to examine the extent to which treatment resulted in changes in nitrate or nitrite concentrations in the brain and altered the brain metabolome. Fish were exposed to sodium nitrate (606.9 mg/L), sodium nitrite (19.5 mg/L), or control water for 2-4 weeks and free swim, startle response, and shuttle box assays were performed. Nitrate and nitrite treatment did not change fish weight, length, predator avoidance, or distance and velocity traveled in an unstressed environment. Nitrate- and nitrite-treated fish initially experienced more negative reinforcement and increased time to decision in the shuttle box assay, which is consistent with a decrease in associative learning or executive function however, over multiple trials, all treatment groups demonstrated behaviors associated with learning. Nitrate and nitrite treatment was associated with mild anxiogenic-like behavior but did not alter epinephrine, norepinephrine or dopamine levels. Targeted metabolomics analysis revealed no significant increase in brain nitrate or nitrite concentrations with treatment. Untargeted metabolomics analysis found 47 metabolites whose abundance was significantly altered in the brain with nitrate and nitrite treatment. Overall, the depletion in brain metabolites is plausibly associated with the regulation of neuronal activity including statistically significant reductions in the inhibitory neurotransmitter γ-aminobutyric acid (GABA; 18-19%), and its precursor, glutamine (17-22%). Nitrate treatment caused significant depletion in the brain concentration of fatty acids including linoleic acid (LA) by 50% and arachidonic acid (ARA) by 80%; nitrite treatment caused depletion of LA by ~90% and ARA by 60%, change which could alter the function of dopaminergic neurons and affect behavior. Nitrate and nitrite treatment did not adversely affect multiple parameters of zebrafish health. It is plausible that indirect NO-mediated mechanisms may be responsible for the nitrate and nitrite-mediated effects on the brain metabolome and behavi

Topics: Animals; Anxiety; Arachidonic Acid; Association Learning; Behavior, Animal; Body Size; Body Weight; Brain; Dopamine; Epinephrine; Executive Function; Female; gamma-Aminobutyric Acid; Glutamine; Linoleic Acid; Male; Metabolome; Nitrates; Norepinephrine; Reflex, Startle; Reinforcement, Psychology; Sodium Nitrite; Zebrafish

Linoleic acid consumption is increasing in Western populations. We investigated whether elevated linoleic acid in pregnancy was deleterious to mothers or offspring. Maternal and fetal body and organ weights were not affected by elevated linoleic acid consumption. Maternal lipids and leptin were altered following elevated linoleic acid consumption. Male offspring numbers were reduced following elevated linoleic acid consumption.. Dietary intakes of linoleic acid (LA) have increased dramatically in Western populations, including in women of reproductive age. Pro-inflammatory effects of LA may have detrimental effects on maternal and offspring outcomes. We aimed to investigate whether consumption of a maternal diet with elevated LA altered maternal inflammatory or metabolic markers during pregnancy, fetal growth and/or the sex ratio of the offspring. Female Wistar Kyoto rats consumed a diet high in LA (HLA) (6.21% of energy) or a diet low in LA (LLA) (1.44% of energy) for 10 weeks prior to mating and during pregnancy. Pregnant rats were killed at embryonic day 20 (E20). There were no differences in maternal or fetal body weights or organ weights in the HLA group compared to the LLA group. There was no difference in maternal circulating cytokine concentrations between dietary groups. In the maternal liver, IL-1α concentrations were significantly lower, and TNF-α and IL-7 significantly higher in the HLA group. Total plasma cholesterol, LDL-cholesterol, HDL cholesterol and the total:HDL cholesterol ratio were lower in dams fed the HLA diet. mRNA expression of sterol regulatory element binding transcription factor 1 (SREBF-1) and leptin in maternal adipose tissue was lower in the HLA group, as were circulating leptin concentrations. The proportion of male fetuses was lower and circulating prostaglandin E metabolite concentrations were increased in the HLA group. In conclusion, consumption of a maternal diet high in linoleic acid alters cholesterol metabolism and prostaglandin E metabolite concentrations, which may contribute to the reduced proportion of male offspring.

Topics: Adipose Tissue; Animals; Biomarkers; Body Weight; Cholesterol; Diet; Female; Fetus; Leptin; Linoleic Acid; Lipid Metabolism; Male; Models, Animal; Organ Size; Pregnancy; Rats; Rats, Inbred WKY

The hypolipidemic effect of phytosterols has been wildely recognized, but its application is limited due to its insolubility in water and low solubility in oil. In this study, β-sitosterol ester with linoleic acids and β-sitosterol self-microemulsions were prepared and their hypolipidemic effects on hyperlipidemia mice were studied.. Firstly, the mice were randomly divided into normal group and model group,they were fed with basic diet and high-fat diet for 70 days respectively. After high-fat model mice was successfully established, the model group was further divided into eight groups: HFD (high-fat diet feeding), SELA-TSO(8 ml/kg, SELA:700 mg/kg), TSO (8 ml/kg), SSSM (8 ml/kg,SS:700 mg/kg), NLSM (8 ml/kg), SSHT-TSO (8 ml/kg, SS: 700 mg/kg) and SS-TSO (8 ml/kg, SS: 700 mg/kg) groups, and treated with β-sitosterol ester with linoleic acid, β-sitosterol self-microemulsion, commercial β-sitosterol health tablets and β-sitosterol powder for 35 days, respectively, and blank control groups were established. At the end of the treatment period, the blood lipid level, tissues, cholesterol and lipids in feces of mice in each group were investigated. Statistical and analytical data with SPSS 17.0 Software,statistical significance was set at p* < 0.05 and p** < 0.01 levels .. The order of lowering blood lipid effect is listed as: SSSM> SELA-TSO > SSHT-TSO > SS-TSO, which shows that β-sitosterolself-microemulsion have the highest treatment effect among the experimental groups.. In this study, a new formulation of β-sitosterol was developed, and its hypolipidemic effect was investigated. The results showed that β-sitosterol self-microemulsion has a good blood lipid lowering effect.

Topics: Administration, Oral; Animals; Body Weight; Eating; Emulsions; Feces; Hyperlipidemias; Hypolipidemic Agents; Linoleic Acid; Lipids; Male; Mice; Microscopy, Electron, Transmission; Organ Size; Sitosterols; Tablets

Fatty acid-induced hypothalamic inflammation (HI) is a potential cause of the obesity epidemic. It is unclear whether saturated or n-6 polyunsaturated fat is the primary driver of these effects. Premenopausal women are protected, in part, from obesity and associated comorbidities by circulating 17β-estradiol (E2). It is unknown how HI interacts with E2, because most studies of HI do not examine females despite the involvement of E2 in hypothalamic energy homeostasis. Our objective is to determine the effects of high-fat diets with varying levels of linoleic acid (LA) and saturated fat on the energy and glucose homeostasis in female mice with and without E2. Female C57BL/6J mice were fed either a control diet or a 45% kilocalories from fat diet with varying levels of LA (1, 15, or 22.5% kilocalories from LA) with or without E2 (300 μg/kg/day orally). After 8 weeks, the oil-treated high-fat groups gained more weight than control groups regardless of fat type. E2 reduced body fat accumulation in all high-fat groups. Glucose clearance from glucose challenge was impaired by LA. Nighttime O

Topics: Adiposity; Animals; Blood Glucose; Body Composition; Body Weight; Diet; Diet, High-Fat; Dietary Fats; Estradiol; Fatty Acids; Female; Homeostasis; Hypothalamus; Interleukin-6; Leptin; Linoleic Acid; Mice; Mice, Inbred C57BL; Obesity; Oxygen Consumption; Weight Gain

In Northern Ghana, 33% of children are stunted due to economic disparities. Dietary fatty acids (FA) are critical for growth, but whether blood FA levels are adequate in Ghanaian children is unknown. The objective of this study was to determine the association between whole blood FAs and growth parameters in Northern Ghanaian children 2-6 years of age. A drop of blood was collected on an antioxidant treated card and analyzed for FA composition. Weight and height were measured and z-scores were calculated. Relationships between FAs and growth parameters were analyzed by Spearman correlations, linear regressions, and factor analysis. Of the 307 children who participated, 29.7% were stunted and 8% were essential FA deficient (triene/tetraene ratio>0.02). Essential FA did not differ between stunted and non-stunted children and was not associated with height-for-age z-score (HAZ) or weight-for-age z-score (WAZ). In hemoglobin adjusted regression models, both HAZ and WAZ were positively associated with arachidonic acid (p≤0.01), dihomo-gamma-linolenic acid (DGLA, p≤0.05), docosatetraenoic acid (p≤0.01) and the ratio of DGLA/linoleic acid (p≤0.01). These data add to the growing body of evidence indicating n-6 FAs are critical in childhood linear growth. Our findings provide new insights into the health status of an understudied Northern Ghanaian population.

Topics: Arachidonic Acid; Body Height; Body Weight; Child; Child, Preschool; Cross-Sectional Studies; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Ghana; Growth Disorders; Hemoglobins; Humans; Linear Models; Linoleic Acid; Male

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease which has no effective treatment and is characterized by psychiatric disorders, motor alterations, and dementia, with the cognitive deficits representing a devastating aspect of the disorder. Oxidative stress and elevated levels of lipid peroxidation (LPO) products are found in mouse models and patients with HD, suggesting that strategies to reduce LPO may be beneficial in HD. In contrast with traditional antioxidants, substituting hydrogen with deuterium at bis-allylic sites in polyunsaturated fatty acids (D-PUFA) decreases the rate-limiting initiation step of PUFA autoxidation, a strategy that has shown benefits in other neurodegenerative diseases. Here, we investigated the effect of D-PUFA treatment in a knock-in mouse model of HD (Q140) which presents motor deficits and neuropathology from a few months of age, and progressive cognitive decline. Q140 knock-in mice were fed a diet containing either D- or H-PUFAs for 5 months starting at 1 month of age. D-PUFA treatment significantly decreased F

Topics: Animals; Body Weight; Cognitive Dysfunction; Deuterium; Dietary Supplements; Disease Models, Animal; Fatty Acids, Unsaturated; Female; Huntingtin Protein; Huntington Disease; Linoleic Acid; Lipid Peroxidation; Male; Mice, Transgenic; Motor Activity

Circulating oxidized linoleic acid (LA) metabolites (OXLAMs) are increased in patients with nonalcoholic steatohepatitis (NASH) and their levels correlate with disease severity. However, the mechanisms by which OXLAMs contribute to NASH development are incompletely understood. We tested the hypothesis that LA or OXLAMs provided directly through the diet are involved in the development of hepatic injury. C57BL/6 mice were fed an isocaloric high-fat diet containing low LA, high LA, or OXLAMs for 8 weeks. The livers of OXLAM-fed mice showed lower triglyceride concentrations, but higher FA oxidation and lipid peroxidation in association with increased oxidative stress. OXLAM-induced mitochondrial dysfunction was associated with reduced Complex I protein and hepatic ATP levels, as well as increased mitochondrial biogenesis and cytoplasmic mitochondrial DNA. Oxidative stress increased thioredoxin-interacting protein (TXNIP) in the liver and stimulated the activation of mitochondrial apoptosis signal-regulating kinase 1 (ASK1) leading to apoptosis. We also found increased levels of NOD-like receptor protein 3 (NLRP3) inflammasome components and Caspase-1 activation in the livers of OXLAM-fed mice. In vitro, OXLAMs induced hepatocyte cell death, which was partly dependent on Caspase-1 activation. This study identified key mechanisms by which dietary OXLAMs contribute to NASH development, including mitochondrial dysfunction, hepatocyte cell death, and NLRP3 inflammasome activation.

Topics: Animals; Apoptosis; Body Weight; Carrier Proteins; Diet, High-Fat; Gene Expression Regulation; Inflammasomes; Linoleic Acid; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Mitochondria, Liver; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Thioredoxins

Linoleic acid (LA, 18:2n-6) is a precursor to arachidonic acid (AA, 20:4n-6), which can be converted by brain lipoxygenase and cyclooxygenase (COX) enzymes into various lipid mediators involved in the regulation of brain immunity. Brain AA metabolism is activated in rodents by the bacterial endotoxin, lipopolysaccharide (LPS). This study tested the hypothesis that dietary LA lowering, which limits plasma supply of AA to the brain, reduces LPS-induced upregulation in brain AA metabolism. Male Fischer CDF344 rats fed an adequate LA (5.2 % energy (en)) or low LA (0.4 % en) diet for 15 weeks were infused with LPS (250 ng/h) or vehicle into the fourth ventricle for 2 days using a mini-osmotic pump. The incorporation rate of intravenously infused unesterified

Topics: Animals; Arachidonic Acid; Body Weight; Brain; Carbon Isotopes; Dietary Fats; Kinetics; Linoleic Acid; Lipopolysaccharides; Male; Rats, Inbred F344; Time Factors

Zinc is an essential micronutrient for humans with important physiological functions. A sensitive and specific biomarker for assessing Zn status is still needed.. The major aim of this study was to examine if the changes in the content of plasma phospholipid LA, DGLA and LA: DGLA ratio can be used to efficiently predict the dietary Zn intake and plasma Zn status of humans.. The study was performed on healthy human volunteers, 25-55 years of age. The dietary Zn intake was assessed using 24 h recall questionnaires. Plasma phospholipid fatty acid analysis was done by gas chromatography, and plasma analysis of minerals by atomic absorption spectrometry. Biochemical, anthropometrical and hematological parameters were assessed.. No significant relationship was found between the dietary and plasma zinc status (r = 0.07; p = 0.6). There was a statistically significant correlation between DGLA and plasma Zn (r = 0.39, p = 0.00). No relationship was observed between the linoleic acid and plasma Zn, while there was a significant negative correlation between LA: DGLA ratio and plasma Zn status (r = -0.35, p = 0.01). Similarly, there were statistically significant difference in DGLA status (p = 0.004) and LA: DGLA ratio (p = 0.042) between the Zn formed groups.. This study is an initial step in evaluating LA: DGLA ratio as a biomarker of Zn status in humans. The results are encouraging as they show that concentration of DGLA is decreased and LA: DGLA ratio increased in people with lower dietary Zn intake. However, additional studies are needed to fully examine the sensitivity of this biomarker.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Biomarkers; Body Mass Index; Body Weight; Diet; Energy Intake; Fatty Acids; Female; Humans; Linoleic Acid; Male; Middle Aged; Nutritional Status; Phospholipids; Zinc

The effect of pasta inclusion in finishing pig diets was evaluated on growth performance, carcass characteristics, and ham quality. Pigs (144) were assigned to 4 diets with different pasta levels: 0 (control, corn-based diet), 30, 60, or 80%. Pigs fed pasta had greater (linear, P<0.01) feed intakes than controls. Pasta increased (quadratic, P<0.01) carcass weight and dressing percentage reaching the highest values at 30% inclusion level, and reduced (linear, P<0.01) the Longissimus thoracis et lumborum thickness. Pasta decreased (linear, P<0.01) linoleic acid and polyunsaturated fatty acid levels in subcutaneous (fresh and seasoned hams) and intramuscular (seasoned hams) fat, and enhanced saturated fatty acid content in subcutaneous fat (fresh hams: quadratic, P<0.01; seasoned hams: linear, P=0.03). Proteolysis index, colour, weight losses, and sensory properties (excepted extraneous taste) of the hams were unaffected by the pasta. Pasta could be considered as an ingredient in the diet for typical Italian finishing heavy pigs.

Topics: Adipose Tissue; Animal Feed; Animals; Body Composition; Body Weight; Diet; Dietary Fats; Edible Grain; Energy Intake; Fatty Acids; Fatty Acids, Unsaturated; Humans; Italy; Linoleic Acid; Meat; Muscle, Skeletal; Subcutaneous Fat; Swine; Triticum; Zea mays

We previously observed that resolvin D1 (RvD1), a metabolite of the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid, reduces infarct size by a mechanism involving the PI3-K/Akt pathway. In parallel, the beneficial effect of a high omega-3 PUFA diet on infarct size can be attenuated by increased omega-6 PUFA consumption. The present study was designed to determine if augmented linoleic acid (LA), an omega-6 PUFA administered at the same time, attenuates the cardioprotective action of RvD1. Male Sprague-Dawley rats received 0.1μg RvD1 alone or with one of three LA doses (1, 5 or 10μg) directly into the left ventricle chamber 5min before ischemia. The animals underwent 40min of ischemia by occlusion of the left descending coronary artery followed by 30min or 24h of reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion, while caspase-3, -8 and -9 and Akt activities were assessed at 30min of reperfusion. LA attenuated cardioprotection afforded by RvD1, resulting in significantly increased infarct size. Neutrophil accumulation and Akt activity were similar between groups. Caspase activities, especially caspase-9, which could be activated by ischemia, were stimulated in the presence of LA, suggesting that this omega-6 PUFA accentuates ischemia intensity. The present results indicate that LA significantly attenuates the beneficial effect of RvD1 on infarct size. Therefore, reduction of omega-6 intake should be considered to maintain the protection afforded by RvD1.

Topics: Animals; Body Weight; Cardiotonic Agents; Caspases; Docosahexaenoic Acids; Hemodynamics; Linoleic Acid; Myocardial Infarction; Rats; Rats, Sprague-Dawley

In Tanzania, 35% of all children below five years of age are stunted. Dietary fatty acids (FA) are critical for growth and development. However, whole blood FA levels in Tanzanian children are poorly described.. The objectives of this cross-sectional study were to assess 1) whole blood levels of essential fatty acids and 2) the association between whole blood FA levels and growth parameters in Tanzanian children 2-6 years of age.. A drop of blood was collected on an antioxidant treated card and analyzed for FA composition. Weight and height were measured and z-scores calculated. Relationships between FAs and growth parameters were analyzed by linear regression.. Of the 334 children that participated, 30.3% were stunted. The average whole blood level of Mead acid was 0.15%. The anthropometric z-score height-for-age (HAZ) was inversely associated with Mead acid, the Mead acid to arachidonic acid (T/T) ratio, and total n-9 FA. Additionally, HAZ was positively associated with linoleic acid and total n-6 FA. BMI-for-age was positively associated with oleic acid, total n-9 FA and T/T ratio but inversely associated with arachidonic acid and total n-6 FA. Weight-for-height was inversely associated with arachidonic acid and total n-6 FAs and positively associated with oleic acid and total n-9 FA. Weight-for-age was not associated with any FA tested. Total n-3 FAs were not associated with any growth parameters measured.. The EFA linoleic acid and the markers of FA deficiency were associated with HAZ, an indicator for stunting in 2-6 year old Tanzanian children. Total n-6, total n-9, and a number of individual FAs were associated with growth. Increasing dietary intake of EFA and n-6 FAs may be a strategy to combat stunting in this population.

Topics: Body Height; Body Weight; Child; Child, Preschool; Cross-Sectional Studies; Female; Growth Disorders; Humans; Linoleic Acid; Male; Tanzania

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients for normal brain development. The principal dietary n-6 and n-3 PUFAs are linoleic acid (LA) and α-linolenic acid (ALA), respectively, We have previously shown that maternal dietary imbalance between these PUFAs, i.e., rich in LA and poor in ALA, affected brain development and increased anxiety-related behavior in the mouse offspring. Here we further addressed sex difference in anxiety-related behavior in the offspring exposed to maternal LA:ALA imbalance. We fed pregnant mice a LA excess/ALA deficient (LA(ex)/ALA(def)) diet, and raised their offspring on a well-balanced LA:ALA diet from an early lactation period. When the offspring were grown to adulthood, they were subjected to behavioral and biochemical analyses. We found that both male and female offspring exposed to the LA(ex)/ALA(def) diet showed increased anxiety-related behavior compared to those exposed to the control diet, which was differently observed between the sexes. The female offspring also exhibited hyperactivity by maternal intake of the LA(ex)/ALA(def) diet. On the other hand, abnormal depressive behavior was undetected in both sexes. We also found that the ratio of n-6 to n-3 PUFAs in the brain was unaffected regardless of maternal diet or offspring's sex. Since the n-6/n-3 ratio is known to influence emotional behavior, it is reasonable to assume that LA:ALA imbalance exposed during brain development is the key for causing enhanced anxiety in adulthood. The present study indicates that maternal dietary imbalance between LA and ALA increases offspring's anxiety-related behavior with a sex-dependent manner.

Topics: alpha-Linolenic Acid; Animals; Anxiety; Body Weight; Brain; Depression; Diet; Feeding Behavior; Female; Linoleic Acid; Male; Maternal Nutritional Physiological Phenomena; Maze Learning; Mice, Inbred C57BL; Motor Activity; Sex Characteristics

The objective was to evaluate the effect of feeding increasing amounts of essential fatty acids (FA) in milk replacer (MR) during the first 60 d of life on growth, health, and immunity of Holstein calves. Calves were born from dams fed low concentrations of total and essential FA during the lasT2 mo of pregnancy. Newborn calves were blocked by sex and parity of the dam and assigned randomly to receive 1 of 4 MR treatments (T). Hydrogenated coconut oil and soybean oil were mixed with emulsifier and commercial MR powder to prepare the following 4 MR containing 0.119 and 0.007 (T1), 0.187 and 0.017 (T2), 0.321 and 0.036 (T3), and 0.593 and 0.076 (T4) g of intake per kg of metabolic body weight (BW(0.75)) of linoleic acid and α-linolenic acid, respectively. At 30 d of life, concentrations of essential FA (linoleic acid and α-linolenic acid) in liver increased, whereas concentrations of C12:0, C14:0, C16:0, and C20:3n-9 decreased linearly with increasing intake of essential FA. Body weight gain and feed efficiency were optimized when male calves consumed T2, whereas gain by female calves tended to increase linearly with increasing intake of essential FA during the first 30 d of age. However, these responses to treatment were not maintained after initiation of concentrate feeding at 31 d of life. Over the 60-d preweaning period, wither and hip heights were improved in both sexes as intake of essential FA increased up to T3. Some measures of health and immunity were affected by replacing some coconut oil with soybean oil. Severity of diarrhea tended to decrease linearly; plasma concentrations of haptoglobin during diarrhea were lower in T2, T3, and T4; phagocytosis by blood neutrophils tended to peak for calves fed T2; in vitro proliferation of stimulated blood lymphocytes was greater for calves fed T2; in vitro stimulated blood cells produced more IFN-γ (up to T3 for males and T2 for females), concentrations of serum IgG against ovalbumin injections were increased in males fed T2 or T3; and skin-fold thickness increased in response to an intradermal antigen injection of all calves fed up to T4. Across sex and under the conditions of the present study, mean daily intakes of linoleic acid between 3 to 5g/d and intakes of α-linolenic acid between 0.3 and 0.6g/d during the first 30 d of life promoted growth of preweaned Holstein calves, possibly by improving their immune status.

Topics: alpha-Linolenic Acid; Animals; Animals, Newborn; Body Weight; Cattle; Coconut Oil; Diet; Fatty Acids, Essential; Female; Linoleic Acid; Male; Milk; Neutrophils; Plant Oils; Soybean Oil; Weaning; Weight Gain

Plasma fatty acids (FAs) and micronutrients have been associated with central obesity in adults; however, previous studies of these associations in adults have yielded mixed results. In addition, no comparable research has been conducted among youth with type 1 diabetes (T1D).. We investigated the cross-sectional and longitudinal associations between plasma nutrient biomarkers and waist-to-height ratio (WHtR) in youth with T1D.. These analyses included 1324 youth aged 3-20 y at T1D diagnosis with a baseline visit in the SEARCH (Search for Diabetes in Youth) Study and a subset of 1178 of these youth with a follow-up visit an average of 23 mo (range: 16-40 mo) after their baseline visit. Plasma phospholipid FAs and vitamins were measured, and estimated desaturase activities were calculated at baseline. Anthropometric measurements and diabetes-related assessments were collected at each visit. Multiple linear regression was used to examine the association between plasma nutrient biomarkers and WHtR.. In cross-sectional analysis, plasma palmitic acid (P = 0.004), dihomo-γ-linolenic acid (DGLA; P = 0.017) and Δ6 desaturase (D6D; P = 0.006) were positively correlated with WHtR after adjustment of confounders. Oleic acid (OA; P = 0.002), linoleic acid (LA; P = 0.015), Δ9 desaturase 18 (D9D-18; P = 0.027), and vitamin D (P < 0.0001) were negatively correlated with WHtR after adjustment. Weight status was an effect modifier (P < 0.05). In normal-weight youth, vitamin D (P = 0.003) was negatively associated with WHtR. In obese youth, stearic acid (P = 0.037), DGLA (P < 0.0001), and D6D (P < 0.0001) were positively associated and OA (P = 0.0008), D9D-18 (P = 0.0006), and vitamin D (P < 0.0001) were negatively associated with WHtR. In longitudinal analysis, baseline linoleic acid (P = 0.018), n-6:n-3 (ω-3:ω-6) FA ratio (P = 0.029), vitamin D (P = 0.003), and vitamin E (P < 0.0001) were negatively correlated with WHtR at follow-up only in obese participants.. In T1D youth, plasma FAs and vitamins are associated with WHtR and are modified by weight status. These associations are particularly marked in obese youth.

Topics: Adolescent; Biomarkers; Body Height; Body Mass Index; Body Weight; Child; Child, Preschool; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Fatty Acid Desaturases; Fatty Acids, Omega-3; Female; Follow-Up Studies; Humans; Limit of Detection; Linoleic Acid; Longitudinal Studies; Male; Micronutrients; Obesity; Palmitic Acid; Phospholipids; Prospective Studies; Vitamin D; Vitamin E; Waist Circumference; Young Adult

Thermally oxidized vegetable ghee was fed to the rabbits for 14 days with specific doses of sea buckthorn seed oil (SO). The ghee and SO were characterized for quality parameters and fatty acid composition using GC-MS. Rabbits serum lipid profile, hematology and histology were investigated. Major fatty acids were palmitic acid (44%) and oleic acid (46%) in ghee, while SO contains oleic acid (56.4%) and linoleic acid (18.7%). Results showed that oxidized vegetable ghee increases the serum total cholesterol, LDL-cholesterols, triglycerides and decrease the serum glucose. Oxidized ghee produced toxic effects in the liver and hematological parameters. Sea buckthorn oil supplementation significantly lowered the serum LDL-cholesterols, triglycerides and increased serum glucose and body weight of the animals. Sea buckthorn oil was found to reduce the toxic effects and degenerative changes in the liver and thus provides protection against the thermally oxidized lipids induced oxidative stress.

Topics: Animals; Blood Glucose; Body Weight; Cholesterol, LDL; Gas Chromatography-Mass Spectrometry; Ghee; Hippophae; Hot Temperature; Linoleic Acid; Lipids; Liver; Oleic Acid; Oxidation-Reduction; Oxidative Stress; Palmitic Acid; Plant Oils; Protective Agents; Rabbits; Seeds; Triglycerides

3-Monochloropropane-1,2-diol (3-MCPD) esters have been detected in many foods, which have become a new safety issue worldwide. In the study, we investigated the effect of four 3-MCPD diesters (palmitate diester: CDP; stearate diester: CDS; oleate diester: CDO; linoleate diester: CDL) on lipid metabolism in C57BL/6J mice. The results showed that CDP, CDS, CDO and CDL significantly increased the serum TC, LDL-C levels and liver TG, TC levels at dose of 16.5μmol/kg/day. These results indicated that 3-MCPD diesters could potentially cause hyperlipidemia in C57BL/6J mice. Moreover, oil red O staining confirmed fat accumulation in liver induced by 3-MCPD diesters. Our work will provide more information for safety evaluation of 3-MCPD diesters. However, whether free 3-MCPD or free fatty acids or combined action compensates for the hyperlipidemia effects should be elucidated in the future.

Topics: alpha-Chlorohydrin; Animals; Biomarkers; Body Weight; Dose-Response Relationship, Drug; Hyperlipidemias; Linoleic Acid; Lipid Metabolism; Lipids; Liver; Male; Mice; Mice, Inbred C57BL; Oleic Acid; Palmitates

Maternal consumption of a high-fat diet significantly impacts the fetal environment and predisposes offspring to obesity and metabolic dysfunction during adulthood. We examined the effects of a high-fat diet during pregnancy and lactation on metabolic and inflammatory profiles and whether maternal supplementation with the anti-inflammatory lipid conjugated linoleic acid (CLA) could have beneficial effects on mothers and offspring. Sprague-Dawley rats were fed a control (CD; 10% kcal from fat), CLA (CLA; 10% kcal from fat, 1% total fat as CLA), high-fat (HF; 45% kcal from fat) or high fat with CLA (HFCLA; 45% kcal from fat, 1% total fat as CLA) diet ad libitum 10days prior to and throughout gestation and lactation. Dams and offspring were culled at either late gestation (fetal day 20, F20) or early postweaning (postnatal day 24, P24). CLA, HF and HFCLA dams were heavier than CD throughout gestation. Plasma concentrations of proinflammatory cytokines interleukin-1β and tumour necrosis factor-α were elevated in HF dams, with restoration in HFCLA dams. Male and female fetuses from HF dams were smaller at F20 but displayed catch-up growth and impaired insulin sensitivity at P24, which was reversed in HFCLA offspring. HFCLA dams at P24 were protected from impaired insulin sensitivity as compared to HF dams. Maternal CLA supplementation normalised inflammation associated with consumption of a high-fat diet and reversed associated programming of metabolic dysfunction in offspring. This demonstrates that there are critical windows of developmental plasticity in which the effects of an adverse early-life environment can be reversed by maternal dietary interventions.

Topics: Animals; Body Weight; Diet; Diet, High-Fat; Dietary Supplements; Female; Gene Expression Profiling; Gene Expression Regulation; Inflammation; Insulin; Insulin Resistance; Interleukin-1beta; Linoleic Acid; Linoleic Acids, Conjugated; Liver; Male; Maternal Nutritional Physiological Phenomena; Obesity; Phenotype; Pregnancy; Pregnancy, Animal; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Following the historical dietary recommendations, the substitution of polyunsaturated fatty acids (PUFAs) for saturated fatty acids (SFAs) resulted in a dramatic increase of linoleic acid (LA) in the Western diet. While proatherogenic properties of SFAs have been described, the involvement of LA on the inflammatory process remains controversial. Herein, we evaluated the effects of an excessive LA intake on the cytokine-induced expression of endothelial adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1), through the nuclear factor (NF)-κB pathway, in comparison with a control diet and regarding a "positive" SFA diet. Wistar rats were fed experimental diets - a control diet or diets enriched with LA or SFA - for 11 weeks. Plasma lipid parameters and proinflammatory cytokine production such as interleukin-1β and tumor necrosis factor (TNF)-α were analyzed. Expression of endothelial adhesion molecules and NF-κB was determined by immunohistochemical analysis. No difference was observed in body weight. The enriched diets did not affect triglyceride and total cholesterol levels in plasma. Our results demonstrated that excessive dietary LA intake increased TNF-α levels (P<.05) in plasma. Rats fed the LA-enriched diet showed a significantly higher expression of VCAM-1, ICAM-1 and NF-κB in aortas. In addition, our results demonstrated that an excess of LA is more efficient to activate endothelial molecular process than an excess of SFA. The present study provides further support for the proinflammatory properties of LA and suggests an LA-derivatives pathway involved in the inflammatory process.

Topics: Animals; Aorta; Body Weight; Cyclooxygenase 2; Diet; Endothelial Cells; Fatty Acids; Immunohistochemistry; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1beta; Linoleic Acid; Lipids; NF-kappa B; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Recently, the pro-inflammatory effects of linoleic acid (LNA) have been re-examined. It is now becoming clear that relatively few studies have adequately assessed the effects of LNA, independent of obesity. The purpose of this work was to compare the effects of several fat-enriched but non-obesigenic diets on inflammation to provide a more accurate assessment of LNA's ability to induce inflammation. Specifically, 8-week-old male C57Bl/6 mice were fed either saturated (SFA), monounsaturated (MUFA), LNA, or alpha-linolenic acid enriched diets (50 % Kcal from fat, 22 % wt/wt) for 4 weeks. Chow and high-fat, hyper-caloric diets were used as negative and positive controls, respectively. Expression of pro-inflammatory and pro-coagulant markers from epididymal fat, liver, and plasma were measured along with food intake and body weights. Mice fed the high SFA, MUFA, and high-fat diets exhibited increased pro-inflammatory markers in liver and adipose tissue; however, mice fed LNA for four weeks did not display significant changes in pro-inflammatory or pro-coagulant markers in epididymal fat, liver, or plasma. The present study demonstrates that LNA alone is insufficient to induce inflammation. Instead, it is more likely that hyper-caloric diets are responsible for diet-induced inflammation possibly due to adipose tissue remodeling.

Topics: Adipose Tissue; Animals; Body Weight; Diet, High-Fat; Inflammation; Linoleic Acid; Liver; Male; Mice; Obesity; Triglycerides

Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA-PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet.

Topics: Adipose Tissue; Analysis of Variance; Animals; Arachidonic Acids; Body Weight; Diet; Diet, Fat-Restricted; Endocannabinoids; Erythrocytes; Fatty Acids; Glycerides; Leptin; Linoleic Acid; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Obesity; Phospholipids; Polyunsaturated Alkamides; Risk Factors; Weight Gain

This study evaluated the effect of a blend of synthetic antioxidants on the yield of milk and milk components and milk fatty acid composition in dairy cows fed a diet designed to cause milk fat depression (MFD). We hypothesized that supplementing a synthetic antioxidant to diets with a high rumen unsaturated fatty acid load (RUFAL) would decrease the severity of MFD. Sixteen lactating Holstein cows (163 ± 47 d in milk), in a crossover design with two 21-d periods, were fed a corn silage and grass silage-based diet containing 15% distillers grains. The diet contained 34% neutral detergent fiber, 18% crude protein, 26% starch, and 4.3% total fatty acids (dry matter basis). Cows were fed the diet without supplementation (control; CON) or supplemented with 0.02% (dry matter basis) of a synthetic antioxidant (AOX; Agrado Plus, Novus International Inc., St. Charles, MO). Dry matter intake and milk yields were recorded daily. Milk samples were collected at the start of the study for baseline values and the end of each period (d 20-21) and analyzed for milk components and fatty acid composition. Dry matter intake and milk yield were unaffected by treatment and averaged 25.9 and 50.2 kg/d, respectively. Similarly, we observed no effect of treatment on yields of fat, protein, lactose, 3.5% fat-corrected milk, energy-corrected milk, feed efficiency, body weight, or body condition score. Milk fat concentration and yield were both reduced by the high RUFAL diets. We observed a tendency for AOX to increase the concentration of milk fat and decrease the concentration of milk protein. Yields of de novo and preformed fatty acids were not affected by treatment, although we detected a trend for a slight increase in the yield of 16-carbon fatty acid for AOX compared with CON. Treatment had only minor effects on individual milk fatty acids, except for the concentration and yield of linoleic acid, which were over 90% higher for AOX compared with CON. In conclusion, milk fat concentration and yield were reduced by a high RUFAL diet containing 15% distillers grains; however, supplementation with AOX did not overcome the MFD induced by this diet.

Topics: Animals; Antioxidants; Body Weight; Cattle; Cross-Over Studies; Dairying; Depression; Diet; Dietary Fiber; Dietary Supplements; Fatty Acids; Female; Lactation; Linoleic Acid; Milk; Milk Proteins; Rumen; Silage; Zea mays

Intestinal nutrient infusions result in variable decreases in food intake and body weight based on the nutrient type and the specific intestinal infusion site. We previously found that intrajejunal infusions of a fatty acid and glucose, but not casein hydrolysate, decreases food intake and body weight in lean chow-fed laboratory rats. To test whether obese, high fat-fed animals would show similar decreases in food intake and body weight in response to intrajejunal infusions of the same nutrients, equal kilocalorie loads of these nutrients (11.4 kcal) or vehicle were infused into the jejunum of obese, high fat-fed male Sprague-Dawley rats over 7 h/day for 5 consecutive days. Food intake was continuously monitored, and body weight was measured daily. After the infusion on the final day, rats were killed and plasma was collected. Similar to lean chow-fed rats, intrajejunal infusions of linoleic acid (LA) and glucose (Glu), but not casein hydrolysate (Cas), suppressed food intake with no compensatory increase in food intake after the infusion period. In contrast to lean chow-fed rats, only the LA, and not the Glu or Cas, produced decreases in body weight in the obese high fat-fed rat. There also were no differences in plasma glucagon-like peptide-1 levels in any of the nutrient infusion groups compared with saline infusion. These results suggest that there is a differential response to the same nutrients in lean vs. obese animals.

Topics: Animals; Body Weight; Caseins; Eating; Endocrine System; Enteral Nutrition; Glucagon-Like Peptide 1; Glucose; Jejunum; Linoleic Acid; Male; Obesity; Peptide YY; Rats; Rats, Sprague-Dawley; Satiation

Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn⁺ (zinc adequate control, 42.3 μg/g zinc), and Zn⁻ (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn⁺ control versus Zn⁻ group (p < 0.05). Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn⁺ control group (p < 0.05), and hepatic Δ⁶ desaturase was significantly higher in the Zn⁺ group (p < 0.001). The LA:DGLA ratio was significantly elevated in the Zn⁻ group compared to the Zn⁺ group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001). This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Biomarkers; Body Weight; Chickens; Diet; Erythrocytes; Fatty Acids; Gene Expression; Interleukin-1beta; Interleukin-6; Linoleic Acid; Liver; Nutritional Status; Phytic Acid; RNA, Ribosomal, 18S; Tumor Necrosis Factor-alpha; Zinc

Ethanol is a dietary factor that dose-dependently increases breast cancer risk in women. We previously have shown that ethanol increases mammary epithelial density through increased branching after dietary exposure during puberty in CD2/F1 mice. To extend these studies to parous mice in a breast cancer model, we used a transgenic mouse model of human parity-associated breast cancer, the FVB-MMTV-Her2/Neu mouse, which overexpresses wildtype EGFR2, resulting in constitutive activation of growth signaling in the mammary epithelium. Here we describe the short-term effects of ethanol feeding on progression through involution. Mice were fed diets supplemented with 0%, 0.5%, 1%, or 2% ethanol for 4, 9, or 14 d starting on day 21 of lactation (that is, at the start of natural postlactational involution). Unlike peripubertal mice exposed to ethanol, postlactational dams showed no changes in body weight; liver, spleen, and kidney weights; and pathology. Ethanol exposure had no effect on mammary gland lobular density and adipocyte size throughout involution. Likewise, the infiltration of inflammatory cells and serum oxidized lipid species were unchanged by diet, suggesting that ethanol feeding had no effect on local inflammation (leukocyte infiltration) or systemic inflammation (oxidized lipids). In conclusion, ethanol exposure of parous dams had no effect on mammary gland structure or the regression of the lactating mammary gland to a resting state. The period of involution that follows natural lactation appears to be refractory to developmental effects of ethanol on mammary epithelium.

Topics: Adipocytes; Analysis of Variance; Animals; Body Weight; Breast Neoplasms; Chromatography, Liquid; Disease Models, Animal; Ethanol; Female; Kidney; Lactation; Linoleic Acid; Linoleic Acids, Conjugated; Liver; Mammary Glands, Animal; Mass Spectrometry; Mice; Mice, Transgenic; Organ Size; Receptor, ErbB-2; Spleen; Time Factors

Cats have limited Δ6 desaturase activity. However, γ-linolenate (GLA) feeding may by-pass the Δ6 desaturase step allowing arachidonate (ARA) accumulation via Δ5-desaturation. Alternatively, high dietary linoleate (LNA) may induce limited Δ6 desaturase also resulting in ARA accumulation. Fatty acid profiles were determined after feeding high LNA, high GLA, or adequate LNA diets. Adult female cats (n = 29) were assigned to one of three groups and fed for 8 weeks. Plasma samples were collected at weeks 0, 2, 4 and 8 for plasma triacylglycerol (TAG), total cholesterol (TC), lipoprotein (LP), and plasma and red blood cell membrane phospholipid fatty acid determinations. Time, but no diet, effects were observed for TAG, TC, and LP fractions at weeks 2 and 4 with significant increases likely due to increased dietary fat. However, all values were within feline normal limits. The GLA diet resulted in increased dihomo-γ-linolenic acid (DGLA) and ARA as early as week 2, supporting a ∆5 desaturase. Further evidence of Δ5 desaturase was found at high dietary LNA with the appearance of a novel fatty acid, 20:3 ∆7, 11, 14, apparently formed via ∆5 desaturation and chain elongation of LNA. However, Δ6 desaturase induction at high dietary LNA concentration was not observed. Cats are able to maintain plasma and red blood cell ARA when fed a practical diet containing GLA using what appears to be an active Δ5 desaturase enzyme.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acid; Body Weight; Cats; Dietary Fats, Unsaturated; Fatty Acid Desaturases; Female; gamma-Linolenic Acid; Gas Chromatography-Mass Spectrometry; Linoleic Acid; Lipid Metabolism; Liver

Advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) are closely associated with colorectal cancer progression. The association between RAGE and AGE in colon carcinogenesis needs to be clarified.. Levels of RAGE and AGE were examined in azoxymethane (AOM)-injected Fischer 344 rats fed a control diet (Group C), a 15 % linoleic acid (LA) diet (Group L), a control diet with 10 % glucose drink (Group G), and a 15 % LA diet with 10 % glucose drink (Group L + G). Group L + G showed the most pronounced increase of body weight, blood sugar, and serum insulin.. The rats in Group L + G showed the most pronounced multiplicity of aberrant crypt foci (ACF) and carcinomas with increased mucosal RAGE and AGE. IEC6 rat intestinal epithelial cells treated with AGE showed increased RAGE expression, which was inhibited by treatment with metformin or losartan. In the AOM-injected rat colon cancer model, the levels of RAGE and AGE, and the multiplicity of ACF and carcinomas, in Group L + G rats were suppressed by treatment with metformin or losartan.. These results suggest that AGE-RAGE induced by high-LA and high-glucose diets substantially enhances colon cancer development; thus, suppression of AGE-RAGE could be a potential target for colon cancer chemoprevention.

Topics: Animals; Azoxymethane; Body Weight; Carcinogens; Cell Culture Techniques; Colon; Colorectal Neoplasms; Diet; Enzyme-Linked Immunosorbent Assay; Glucose; Glycation End Products, Advanced; Immunoblotting; Immunohistochemistry; Intestinal Mucosa; Linoleic Acid; Male; Rats; Rats, Inbred F344; Receptor for Advanced Glycation End Products; Receptors, Immunologic

This study examined whether purified fish oil (PFO) supplemented to an essential fatty acid deficient (EFAD) diet meets EFA needs in rats. The EFAD diet contained 10% hydrogenated coconut oil (HCO). A similar diet contained 7% HCO and 3% PFO which also provided 2.84% arachidonic acid (AA), 52.50% eicosapentaenoic acid (EPA) and 35.73% docosahexaenoic acid (DHA) but no linoleic acid (LA) or alpha linolenic acid (ALA). A 10% soybean oil control diet provided ample LA and ALA. After 4 weeks of feeding, blood glucose, plasma triglyceride and phospholipid fatty acid profiles, C-reactive protein (CRP), TNF and IL-6 were determined after saline or LPS injection. EFAD developed with the HCO diet with triene:tetraene ratios in plasma phospholipids >.20, which remained <.02 with the control and HCO+PFO diets. Mead acid levels significantly increased by a factor of 10 with the HCO diet compared to the AIN and HCO+PFO diets and were significantly lowest with the HCO+PFO diet. 18:1 n9 levels were significantly higher in plasma phospholipids and triglycerides with the HCO diet. CRP levels were significantly highest with the control diet and significantly lowest with the HCO diet. LPS significantly increased 18:1 n9 and cytokines, and decreased AA and plasma glucose in all diets and significantly increased plasma triglycerides and decreased plasma glucose in controls. Providing AA, EPA and DHA in EFAD prevents EFAD over the short-term as reflected in Mead acid production, triene:tetraene ratio, and de novo lipogenesis and may reduce the inflammatory response to LPS.

Topics: alpha-Linolenic Acid; Animals; Blood Glucose; Body Weight; C-Reactive Protein; Eating; Fish Oils; Interleukin-6; Linoleic Acid; Male; Phospholipids; Rats; Rats, Sprague-Dawley; Triglycerides; Tumor Necrosis Factor-alpha

Two experiments were conducted to determine the effects of sunflower seed supplements with varying fatty acid profiles on performance, reproduction, intake, and digestion in beef cattle. In Exp. 1, 127 multiparous spring-calving beef cows with free-choice access to bermudagrass hay were individually fed 1 of 3 supplements for an average of 83 d during mid to late gestation. Supplements (DM basis) included 1) 1.23 kg/d of a soybean hull-based supplement (control treatment); 2) 0.68 kg/d of linoleic sunflower seed plus 0.23 kg/d of the control supplement (linoleic treatment); and 3) 0.64 kg/d of mid-oleic sunflower seed plus 0.23 kg/d of the control supplement (oleic treatment). During the first 62 d of supplementation, the BW change was 11, 3, and -3 kg for cows fed the control, linoleic, and oleic supplements, respectively (P < 0.001). No difference in BW change was observed during the subsequent period (-65 kg, P = 0.83) or during the entire 303-d experiment (-31 kg, P = 0.49). During the first 62 d of supplementation, cows fed sunflower supplements tended (P = 0.08) to lose more body condition than cows fed the control diet, but BCS was not different (P > 0.22) for any subsequent measurement. At the beginning of the breeding season, the percentage of cows exhibiting luteal activity was greater for cows fed the control diet (43%; P = 0.02) than for cows fed either linoleic (20%) or oleic (16%) supplementation; however, first-service conception rate (67%; P = 0.22) and pregnancy rate at weaning (92%; P = 0.18) were not different among supplements. No differences were detected in calf birth (P = 0.46) or weaning BW (P = 0.74). In Exp. 2, 8 ruminally cannulated steers were used to determine the effects of sunflower seed supplementation on forage intake and digestion. Treatments (DM basis) included 1) no supplement; 2) a soybean hull-based supplement fed at 0.29% of BW/d; 3) whole linoleic sunflower seed fed at 0.16% of BW/d; and 4) whole high-oleic sunflower seed fed at 0.16% of BW/d. Hay intake was not influenced (P = 0.25) by supplement (1.51% of BW/d); however, DMI was greatest (P < 0.01) for steers fed the soybean hull-based supplement (1.93% of BW/d). Sunflower seed supplementation reduced (P < 0.01) NDF and ADF digestibility while increasing (P < 0.01) apparent CP and apparent lipid digestibility. In conclusion, whole sunflower seed supplementation resulted in reduced cow BW gain during mid to late gestation, but this reduction did not influence subse

Topics: Animals; Animals, Newborn; Birth Weight; Body Weight; Cattle; Corpus Luteum; Dietary Supplements; Digestion; Eating; Female; Helianthus; Least-Squares Analysis; Linoleic Acid; Male; Oleic Acid; Pregnancy; Random Allocation; Seeds

Intestinal nutrient infusions result in variable decreases in food intake and body weight based on the nutrient type and the specific intestinal infusion site. Only intrajejunal infusions of fatty acids decrease food intake beyond the calories infused. To test whether this extra-compensatory decrease in food intake is specific to fatty acids, small volume intrajejunal infusions of glucose (Glu) and casein hydrolysate (Cas), as well as linoleic acid (LA) were administered to male Sprague-Dawley rats. Equal kilocalorie (kcal) loads of these nutrients (11.4) or vehicle were infused into the jejunum over 7 h/day for five consecutive days. Food intake was continuously monitored and body weight was measured daily. After the infusion on the final day, rats were killed and plasma collected. Intrajejunal infusions of LA and Glu, but not Cas, suppressed food intake beyond the caloric load of the infusate with no compensatory increase in food intake after the infusion period. Rats receiving LA and Glu infusions also lost significant body weight across the infusion days. Plasma glucagon-like peptide-1 (GLP-1) was increased in both the LA and Glu rats compared with control animals, with no significant change in the Cas-infused animals. Peptide YY (PYY) levels increased in response to LA and Cas infusions. These results suggest that intrajejunal infusions of LA and Glu may decrease food intake and body weight via alterations in GLP-1 signaling. Thus, particular nutrients are more effective at producing decreases in food intake, body weight, and inducing changes in peptide levels and could lead to a novel therapy for obesity.

Topics: Analysis of Variance; Animals; Body Weight; Caseins; Eating; Energy Intake; Enzyme-Linked Immunosorbent Assay; Glucagon-Like Peptide 1; Glucose; Jejunum; Leptin; Linoleic Acid; Male; Peptide YY; Radioimmunoassay; Rats; Rats, Sprague-Dawley

Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg x d), or MYR (0.3 mg/kg x d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance.

Topics: Animals; Blood Glucose; Body Weight; Cell Line; Ceramides; Dietary Fats; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Glucose Intolerance; Immunosuppressive Agents; Insulin; Linoleic Acid; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Myoblasts; Oxidoreductases; Palmitates; Pentoxifylline; Phosphatidic Acids; Triglycerides

1. A study was conducted to evaluate how body weight and age of each female are related to the number and physical and chemical characteristics of the eggs produced throughout a breeding season in a captive-bred population of Greater Rheas (Rhea americana). 2. Reproductive performance of 15 females of three age classes (5 individuals per class) was monitored; female body weight was recorded before laying-onset. All the eggs laid were collected and identified, and different morphometric variables, percentage of components and fatty acid composition were determined. 3. The earlier the female started egg-laying, the longer the laying period and the greater the overall number of eggs produced. The onset of egg-laying in turn seemed to be related to the attainment of a high body weight. 4. Except for length, the values of the morphometric variables of the egg and unsaturated fatty acids (palmitoleic, oleic and linoleic) increased with female age. 5. High body weight was associated with low palmitic and palmitoleic fatty acids and high linoleic, linolenic and total unsaturated fatty acids. 6. Live weight and age of females can determine several physical and chemical characteristics of eggs.

Topics: Age Factors; Animals; Body Weight; Clutch Size; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; Linoleic Acid; Ovum; Palmitic Acid; Reproduction; Rheiformes; Time Factors

Animal studies have shown that fatty acids (FA) are important for normal bone development. Human data are scanty and mostly related to diseases. We hypothesised that serum FA pattern might be related to bone mineralisation in healthy children. Serum phospholipid FA pattern was studied in relation to bone parameters in eighty-five healthy Caucasian 8-year-olds. Dual-energy X-ray absorptiometry and blood sampling for analysis of serum phospholipid FA by capillary GLC were performed on the same day. SFA concentrations were associated with bone mineral density (BMD) of the hip, lumbar spine and total body. There was a general trend that linoleic acid (LA; 18 : 2n-6) was negatively associated with BMD, since that was found both for the LA concentration, the total n-6 concentration and the ratio of n-6:n-3 FA. Arachidonic acid (AA; 20 : 4n-6) was positively correlated with bone mineral content (BMC) and BMD of total body, as was the corresponding z-score and the AA:LA ratio. Both saturated and polyunsaturated serum phospholipid FA were associated with BMC and BMD in healthy children. LA and AA were found to inversely influence bone mineralisation and the association with the n-6:n-3 ratio suggested that this balance might also be of importance. The general trend of a negative influence of high n-6 FA concentrations on bone mineralisation might be of concern in relation to the changes in the Western diet. Longitudinal studies are necessary to verify if different bone compartments and different grades of modelling are related to different FA patterns.

Topics: Absorptiometry, Photon; Arachidonic Acid; Biomarkers; Body Mass Index; Body Weight; Bone Density; Bone Development; Calcium; Child; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Linoleic Acid; Lumbar Vertebrae; Male; Vitamin D; Vitamins

Reduced levels of circulating sex hormone-binding globulin (SHBG) are implicated in the etiology of sex steroid-related pathologies and the metabolic syndrome. Dietary correlates of serum SHBG remain unclear and were studied in a convenient cross-sectional sample of healthy 30- to 40-y-old women (n = 255). By univariate analyses, serum SHBG correlated negatively with several indices of the metabolic syndrome, such as BMI, waist circumference, hip circumference (r = -0.36 to -0.44; P < 0.0001), fasting serum insulin (r = -0.41; P < 0.0001), serum triglycerides (r = -0.27; P < 0.0001), serum glucose (r = -0.23; P < 0.001), and plasma testosterone (r = -0.19; P = 0.002). Serum SHBG correlated positively with serum HDL-cholesterol (r = 0.33; P < 0.0001), plasma progesterone (r = 0.17; P = 0.007), and dietary intake of beta-tocopherol (r = 0.17; P = 0.006), and negatively with that of fructose (r = -0.13; P = 0.04). Principal component analysis (PCA) extracted 12 nutrient factors with eigenvalues > 1.0 from 54 nutrients and vitamins in food records. Multivariate regression analyses showed that the PCA-extracted nutrient factor most heavily loaded with beta-tocopherol and linoleic acid (P = 0.03) was an independent positive predictor of serum SHBG. When individual nutrients were the predictor variables, beta-tocopherol (P = 0.002), but not other tocopherols or fatty acids (including linoleic acid), was an independent positive predictor of serum SHBG. Circulating insulin (P = 0.02) and waist circumference (P = 0.002), but not serum lipids, were negative independent predictors of SHBG in all regression models. Additional studies are needed in women of other age groups and men to determine whether consumption of foods rich in beta-tocopherol and/or linoleic acid may increase serum SHBG concentrations and may thereby decrease the risk for metabolic syndrome and reproductive organ cancer.

Topics: Adult; beta-Tocopherol; Body Weight; Cross-Sectional Studies; Diet; Female; Humans; Insulin; Linoleic Acid; Premenopause; Principal Component Analysis; Sex Hormone-Binding Globulin; Waist Circumference

Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil may prevent development of heart failure through alterations in cardiac phospholipids that favorably impact inflammation and energy metabolism. A high-fat diet may block these effects in chronically stressed myocardium. Pathological left ventricle (LV) hypertrophy was generated by subjecting rats to pressure overload by constriction of the abdominal aorta. Animals were fed: (1) standard diet (10% of energy from fat), (2) standard diet with EPA+DHA (2.3% of energy intake as EPA+DHA), (3) high fat (60% fat); or (4) high fat with EPA+DHA. Pressure overload increased LV mass by approximately 40% in both standard and high-fat diets without fish oil. Supplementation with fish oil increased their incorporation into cardiac phospholipids, and decreased the proinflammatory fatty acid arachidonic acid and urine thromboxane B(2) with both the standard and high-fat diet. Linoleic acid and tetralinoloyl cardiolipin (an essential mitochondrial phospholipid) were decreased with pressure overload on standard diet, which was prevented by fish oil. Animals fed high-fat diet had decreased linoleic acid and tetralinoloyl cardiolipin regardless of fish oil supplementation. Fish oil limited LV hypertrophy on the standard diet, and prevented upregulation of fetal genes associated with heart failure (myosin heavy chain-beta and atrial natriuetic factor). These beneficial effects of fish oil were absent in animals on the high-fat diet. In conclusion, whereas treatment with EPA+DHA prevented tetralinoloyl cardiolipin depletion, LV hypertrophy, and abnormal genes expression with pressure overload, these effects were absent with a high-fat diet.

Topics: Animals; Aorta, Abdominal; Arachidonic Acid; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cardiolipins; Cardiotonic Agents; Constriction; Dietary Fats; Docosahexaenoic Acids; Echocardiography; Eicosapentaenoic Acid; Fish Oils; Hypertrophy, Left Ventricular; Linoleic Acid; Male; Myocardium; Myosin Heavy Chains; Organ Size; Phospholipids; Rats; Rats, Wistar; Thromboxane B2

This study investigated the extent to which the increase in torpor expression in the grey mouse lemur, due to graded food restriction, is modulated by a trade-off between a whole body sparing of polyunsaturated dietary fatty acids and the related oxidative stress generated during daily torpor. We measured changes in torpor frequency, total energy expenditure (TEE), linoleate (polyunsaturated fatty acid) and palmitate (saturated fatty acid) oxidation, hexanoyl-lysine (HEL; the product of linoleate peroxidation), and 8-hydroxydeoxyguanosine (8OHdG; a marker of DNA damage). Animals under summer-acclimated long days (LD) or winter-acclimated short days (SD) were exposed to a 40% (LD40 and SD40) and 80% (LD80 and SD80) 35-day calorie restriction (CR). During CR, all groups reduced their body mass, but LD80 animals reached survival-threatened levels at day 22 and were then excluded from the CR trial. Only SD mouse lemurs increased their torpor frequency with CR and displayed a decrease in their TEE adjusted for fat-free mass. After CR, SD40 mouse lemurs shifted the dietary fatty acid oxidation toward palmitate and spared linoleate. Such a shift was not observed in LD animals and during severe CR, during which oxidation of both dietary fatty acids was increased. Concomitantly, HEL increased in both LD40 and SD80 groups, whereas DNA damage was only seen in SD80 food-restricted animals. HEL correlated positively with linoleate oxidation confirming in vivo the substrate/product relationship demonstrated in vitro, and negatively with TEE adjusted for fat-free mass, suggesting higher oxidative stress associated with increased torpor expression. This suggests a seasonal-dependant, cost-benefit trade-off between maximizing torpor propensity and minimizing oxidative stress that is associated with a shift toward sparing of dietary polyunsaturated fatty acids that is dependent upon the expression of a winter phenotype.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; Body Weight; Caloric Restriction; Cheirogaleidae; Deoxyguanosine; Dietary Fats; DNA Damage; Energy Metabolism; Food Deprivation; Hibernation; Linoleic Acid; Lysine; Male; Oxidation-Reduction; Oxidative Stress; Palmitic Acid; Phenotype; Photoperiod; Seasons

Docosahexaenoic acid (DHA) may have potential anticarcinogenic effect. In the present study, effect of DHA on rat C6 glioma was tested. In vitro, cytotoxic effect of 50-400 microM DHA on C6 cells was evaluated and compared with linoleic acid (LA). In vivo, adult female Wistar rats implanted with C6 tumor, fed 1 ml of DHA oil (containing 73% DHA, 36 rats) or LA oil (containing 72-77% LA, 41 rats) daily, starting one week prior to tumor implantation until death or if survived, until 30 days after implantation. Another group of tumor bearing rats was treated with chloroethyl-cyclohexyl-nitrosourea (CCNU, 30 mg/kg, 31 rats) at day 8 post implantation to show if the result of oil supplementation is comparable to single agent chemotherapy. mRNA expression of p21 and p27 was determined in vitro at 100 and 150 microM of fatty acids and in tumors of rats supplemented with LA or DHA oils. In vitro, DHA, but not LA, had cytotoxic effect on C6 cells at 200 and 400 microM and DHA increased mRNA expression of p21 at 150 microM (p < 0.05). In rat glioma model, although a non-significant trend towards better survival was observed in DHA oil relative to LA oil group, the difference was not significant (p = 0.20). p21 and p27 mRNA expression in tumors of DHA oil group did not differ with LA oil group. Single dose of CCNU increased survival when compared to LA oil group (p < 0.001). In conclusion, intake of DHA at the dose or duration employed in the present study might be insufficient to bring about its cytotoxic action on rat's C6 brain tumor.

Topics: Animals; Antineoplastic Agents; Body Weight; Brain Neoplasms; Cell Line, Tumor; Cell Survival; Cyclin-Dependent Kinase Inhibitor p27; Diet; Docosahexaenoic Acids; Eating; Fatty Acids; Female; Glioma; Linoleic Acid; Neoplasm Transplantation; p21-Activated Kinases; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Analysis

To analyze the effects of high-fat high-sucrose (HFHS) feeding, energy restriction, and trans-10,cis-12 conjugated linoleic acid (CLA) on visfatin and apelin.. A randomized dietary intervention study.. Free-living individuals studied in metabolic cages.. Thirty-two male Syrian Golden hamsters (82.6 +/- 1.4 g).. Standard and HFHS feeding for 7 weeks. After that, some hamsters fed the HFHS diet were submitted for 3 weeks to a 25% energy restriction with or without trans-10,cis-12 CLA supplementation (0.5%).. Feeding animals an HFHS diet resulted in increased body fat and reduced insulin sensitivity. No changes were observed in the expression and serum levels of visfatin and apelin, or in peroxisome proliferator-activated receptor (PPAR)gamma and Sirt1 expression. Energy restriction reduced body fat and normalized insulin sensitivity. Visfatin showed increased serum levels without changes in expression. No modifications were found as far as apelin was concerned. Sirt1 expression was increased, and PPARgamma remained unchanged. With regard to trans-10,cis-12 CLA, no changes were induced by its addition to the restricted diet.. Insulin function impairment induced by HFHS feeding is not mediated by visfatin and apelin. However, visfatin can play a role in improving insulin sensitivity associated with energy restriction. These results suggest that visfatin may not have evolved as a molecule that reserves the action of insulin when food is widely available, but rather that its function seems to be associated with energy restriction adaptation. In general terms, trans-10,cis-12 CLA did not modify changes induced by energy restriction.

Topics: Adipose Tissue; Analysis of Variance; Animals; Body Weight; Carrier Proteins; Cricetinae; Dietary Fats; Dietary Sucrose; Enzyme-Linked Immunosorbent Assay; Insulin; Insulin Resistance; Leptin; Linoleic Acid; Male; Mesocricetus; Nicotinamide Phosphoribosyltransferase; PPAR gamma; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction

The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain 'A' mice exposed to 10 Gy whole-body gamma radiation. Animals were treated with 10 and 15 mg/kg b wt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of gamma-radiation (10 Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD(50) and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72 h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of gamma-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection. A single dose of REC-2001 (10 and 15 mg/kg b wt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75 mg/kg b wt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90 mg/kg b wt, resulted in 50% mortality (LD(50)), while the LD(100) was 115 mg/kg b wt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10 Gy radiation resulted in increased halo diameter (45+/-3 microm) in comparison to untreated controls (8+/-1 microm). REC-2001 administration (500 microg/ml) decreased the halo diameter to 15+/-2 microm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of gamma-radiation after further investigations in higher animal models.

Topics: Animals; Berberidaceae; Body Weight; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Gamma Rays; Kaplan-Meier Estimate; Linoleic Acid; Maximum Tolerated Dose; Mice; Phytotherapy; Radiation Injuries, Experimental; Radiation-Protective Agents; Reactive Oxygen Species; Spleen; Whole-Body Irradiation

A number of human and animal studies using conjugated linoleic acids (CLA) or diacylglycerol (DAG) oil have shown positive physiological effects on abdominal adiposity, plasma triglycerides, plasma glucose, and insulin sensitivity. A novel DAG composition containing CLA called CLA diacylglyceride (CLA-DAG) may offer potential as a therapeutic agent in reducing some of the symptoms associated with the diabetic phenotype and metabolic syndrome. This study was designed to investigate the effect of CLA-DAG oil on the diabetic phenotype in male Zucker diabetic fatty rats. Animals were assigned to one of four groups: control (C), rosiglitazone (ROS), CLA-DAG, or CLA as free fatty acid (CLA-FFA). After 11 weeks, body weight was higher and kidney weight was lower in the CLA-DAG and ROS groups compared with the C group. The ROS treatment increased the percentage of body fat as compared with all other groups. Final fasting blood glucose was lower in the CLA-DAG and ROS groups than in the C group. Plasma cholesterol was lower in the CLA-DAG group, and plasma triglycerides were lower in the ROS group compared with the C group. We also observed changes in transcript abundance of PPAR-gamma, PPAR-alpha, FAS, LPL, UCP2, UCP3, CPT1, RxR, ObRb, ApoAII, ApoD, and IRS1 in liver, muscle, and adipose tissue, suggesting treatment-induced effects on these genes. Collectively, these data suggest the need for further research on the therapeutic relevance of CLA-DAG oil in obesity and diabetes. Future research should also differentiate between CLA alone and DAG alone compared with the combination.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diglycerides; DNA, Complementary; Eating; Gene Expression; Hypoglycemic Agents; Insulin; Insulin Resistance; Kidney; Linoleic Acid; Liver; Muscle, Skeletal; Myocardium; Phenotype; Rats; Rats, Zucker; Reverse Transcriptase Polymerase Chain Reaction; Rosiglitazone; Thiazolidinediones; Triglycerides

Hyperlipidemia is the major risk factors of heart disease such as atherosclerosis, stroke, and death. In the present study, we studied the effect of gallic acid (GA), linoleic acid (LA), mixture of GA and LA (MGL), and chemically synthesized gallic acid-linoleic acid ester (octadeca-9,12-dienyl-3,4,5-trihydroxybenzoate, GLE) on the ability to ameliorate hyperlipidemia in C57BL/6 mice fed a high-fat diet (HFD). GLE, GA, LA, and MGL were mixed with HFD and the composition of the test compounds were 1% of the diet for 7 weeks. After 7 weeks, the average body weight of ND and GLE groups was lower than that of HFD group (P<0.05). The liver weight of mice decreased (P<0.05) in all treatment groups relative to HFD fed group. The plasma lipids such as triglyceride and LDL-cholesterol were found to be decreased (P<0.05) in GLE, GA, LA, and MGL fed mice when compared to that of HFD fed mice. But high-density lipoprotein (HDL) cholesterol increased (P<0.05) in HFD and GLE fed mice when compared to that of ND fed mice. The hepatic accumulation of fat droplets of GA, LA, GLE, and MGL group showed considerably lower than that of HFD group. Adipose histology showed that GLE supplementation was found to be more effective in decreasing the size of adipocyte relative to those of other treatment groups. In conclusion, the supplementation of synthetic GLE from gallic acid and linoleic acid ester may have a potential hypolipidemic effect on mice fed high-fat diet. Further studies are required to prove GLE as a hypolipidemic agent.

Topics: Adipocytes; Adipose Tissue; Animals; Body Weight; Cell Nucleus; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Disease Models, Animal; Fatty Liver; Female; Gallic Acid; Hyperlipidemias; Hypolipidemic Agents; Linoleic Acid; Lipids; Liver; Mice; Mice, Inbred C57BL; Obesity; Triglycerides

Children with cystic fibrosis (CF) and pancreatic insufficiency (PI) are at increased risk for essential fatty acid (EFA) deficiency.. To investigate serum markers of EFA status in children with CF and PI and their association with growth, body composition, and lung function.. Serum phospholipid fatty acid, growth, and forced expiratory volume at 1 second (FEV1, percentage predicted) status were assessed at baseline and 12 months in 77 children with CF and PI, 7 to 10 years old. Longitudinal mixed-effects models were used to compare associations of the triene:tetraene ratio (ratio of eicosatrienoic acid to arachidonic acid) and serum linoleic acid (as a molar percentage of total serum phospholipid fatty acids, or mol%) with the clinical outcomes. Controls for serum fatty acid were 23 healthy white age- and sex-matched children.. Children with CF and PI had higher median triene:tetraene ratio and lower linoleic acid than healthy controls. Depending on the triene:tetraene ratio cutoff point used (0.04 or 0.02), either 17% or 52% of the children with CF had EFA deficiency, respectively. Only linoleic acid was significantly and positively associated with z scores for weight, height, body mass index, upper arm muscle area, and FEV1 at baseline. Children with linoleic acid at 21 mol% or higher had significantly better growth and pulmonary status than those with lower concentrations.. Serum phospholipid linoleic acid at 21 mol% or higher was associated with better growth, body composition, and FEV1. No clinical outcome associations were found with the triene:tetraene ratio. These findings suggest that linoleic acid concentration was a more clinically relevant biomarker of EFA status than the triene:tetraene ratio in children with CF and PI. Further research is warranted to validate this specific percentage of linoleic acid cutoff point as a new recommendation for clinical use.

Topics: Adipose Tissue; Biomarkers; Body Composition; Body Mass Index; Body Weight; Child; Cystic Fibrosis; Energy Intake; Fatty Acids, Essential; Female; Genotype; Humans; Linoleic Acid; Male; Phospholipids; Reference Values

To investigate the relationship between chemical structure and physiological effect, the efficacy and the molecular mechanisms involved in the reduction of body weight by C18 fatty acids (stearic, elaidic, oleic, linoleic and 2-hydroxyoleic acids (2-OHOA)).. Ad libitum fed, lean Wistar Kyoto rats treated orally with up to 600 mg kg(-1) of the fatty acids or vehicle every 12 h for 7 days. Besides, starved rats and rats pairfed to the 2-OHOA-treated group served as additional controls under restricted feeding conditions.. Body weight, food intake, weight of various fat depots, plasma leptin, hypothalamic neuropeptides, uncoupling proteins (UCP) in white (WAT) and brown adipose tissue (BAT) and phosphorylation level of cyclic AMP (cAMP) response element-binding protein (CREB) in WAT.. Only treatment with oleic acid and 2-OHOA induced body weight loss (3.3 and 11.4%, respectively) through reduction of adipose fat mass. Food intake in these rats was lower, although hypothalamic neuropeptide and plasma leptin levels indicated a rise in orexigenic status. Rats pairfed to the 2-hydroxyoleic group only lost 6.3% body weight. UCP1 expression and phosphorylation of CREB was drastically increased in WAT, but not BAT of 2-OHOA-treated rats, whereas no UCP1 expression could be detected in WAT of rats treated with oleic acid.. Both cis-configured monounsaturated C18 fatty acids (oleic acid and 2-OHOA) reduce body weight, but the introduction of a hydroxyl group in position 2 drastically increases loss of adipose tissue mass. The novel molecular mechanism unique to 2-hydroxyoleic, but not oleic acid, implies induction of UCP1 expression in WAT by the cAMP/PKA pathway-dependent transcription factor CREB, most probably as part of a transdifferentiation process accompanied by enhanced energy expenditure.

Topics: Adipose Tissue; Animals; Body Weight; Fatty Acids; Feeding Behavior; Immunoblotting; Leptin; Linoleic Acid; Neuropeptides; Oleic Acid; Oleic Acids; Random Allocation; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Stearic Acids; Structure-Activity Relationship

Conjugated Linoleic Acid (CLA) is fatty acid found endogenously in food sources that prevents new tumor development and reduces the growth of existing tumors in laboratory animals. CLA exerts its anti-carcinogenic effect by reducing VEGF and bFGF serum levels and by blocking flk-1 receptors, thereby inhibiting vascular growth critical to tumor growth and survival. Although the ability of CLA to inhibit angiogenesis in the peripheral nervous system is well characterized, it remains unknown whether CLA also affects vascular morphology in the central nervous system. Therefore, in the present study, exercising and sedentary animals received either standard rat chow or a specially formulated diet consisting of 0.5% CLA for 24 days. The brains were then examined to determine the extent of vascular growth in the cerebellum, a region known to exhibit robust exercise-induced angiogenesis. Our results indicate that CLA administration significantly reduces angiogenesis in the cerebellum. This study is the first to demonstrate the anti-angiogenic effect of CLA in the brain, and suggests that CLA be explored as a therapeutic treatment for cancer and tumors in the brain.

Topics: Administration, Oral; Analysis of Variance; Angiogenesis Inhibitors; Animals; Blood Vessels; Body Weight; Brain Injuries; Cerebellum; Eating; Female; Linoleic Acid; Locomotion; Neovascularization, Pathologic; Neovascularization, Physiologic; Rats; Rats, Long-Evans

Alcoholic fatty liver results from an impaired fatty acid catabolism due to blockade of PPARalpha and increased lipogenesis due to activation of sterol regulatory element-binding protein (SREBP)-1c. Because both oxidized fats (OF) and conjugated linoleic acids (CLA) have been demonstrated in rats to activate hepatic PPARalpha, we tested the hypothesis that these fats are able to prevent ethanol-induced triacylglycerol accumulation in the liver by upregulation of PPARalpha-responsive genes. Forty-eight male rats were assigned to 6 groups and fed isocaloric liquid diets containing either sunflower oil (SFO) as a control fat, OF prepared by heating of SFO, or CLA, in the presence and absence of ethanol, for 4 wk. Administration of ethanol lowered mRNA concentrations of PPARalpha and the PPARalpha-responsive genes medium chain acyl-CoA dehydrogenase, long chain acyl-CoA dehydrogenase, acyl-CoA oxidase, carnitine palmitoyl-CoA transferase I, and cytochrome P450 4A1 and increased triacylglycerol concentrations in the liver (P < 0.05). OF increased hepatic mRNA concentrations of PPARalpha-responsive genes and lowered hepatic triacylglycerol concentrations compared with SFO (P < 0.05) whereas CLA did not. Rats fed OF with ethanol had similar mRNA concentrations of PPARalpha-responsive genes and similar triacylglycerol concentrations in the liver as rats fed SFO or CLA without ethanol. In contrast, hepatic mRNA concentrations of SREBP-1c and fatty acid synthase were not altered by OF or CLA compared with SFO. This study shows that OF prevents an alcohol-induced triacylglycerol accumulation in rats possibly by upregulation of hepatic PPARalpha-responsive genes involved in oxidation of fatty acids, whereas CLA does not exert such an effect.

Topics: Animals; Base Sequence; Body Weight; Dietary Fats; DNA Primers; Energy Intake; Ethanol; Linoleic Acid; Liver; Male; PPAR alpha; Rats; Rats, Sprague-Dawley; Triglycerides

Dietary conjugated linoleic acid (CLA) has been investigated for its beneficial effects on disease prevention and treatment, and now obesity is one of the most perspective researching highlights. In a variety of experimental models, the results of studies on the effects of CLA on food intakes are somewhat inconsistent. Our experiment was conducted to extend these observations to hypothalamus and other regions within the central nervous system so that the mechanism of the actions of CLA might be more easily elucidated. In the experiment, a permanent cannula was inserted into the lateral ventricle of each rat. For the experiment, animals received intracerebroventricular injections of either 150nmol (n=16) CLA, or LA as non-conjugated control, or normal saline as vehicle. Hypothalamus and blood samples were collected at the 2nd, 4th, 8th, and 14th day. The results show that CLA in cerebral ventricle can inhibit food intake of experimented rats and this inhibition is related with the decreased expression of neuropeptides Y (NPY) and agouti-related protein (AgRP). The circulating leptin level was also increased by this tentative treatment (2.94+/-0.71 versus 1.18+/-0.18ng/ml). However, the glucose metabolism was not affected by ICV CLA. It is concluded that CLA in brain can inhibit the appetite of rats through the mechanism of decreasing the expression of NPY and AgRP.

Topics: Agouti-Related Protein; Animals; Behavior, Animal; Body Weight; Down-Regulation; Injections, Intraventricular; Intercellular Signaling Peptides and Proteins; Linoleic Acid; Male; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors

During tryptophan-niacin conversion, hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) [EC4.1.1.45] plays a key role in regulating NAD biosynthesis. ACMSD activity is greatly affected by many factors such as nutritional status and disease. The tryptophan catabolite quinolinic acid has been reported to be associated with the pathogenesis of various disorders and is a potential endogenous toxin. However the effects of dietary protein levels or dietary interaction between protein levels and fatty acid type to this process have not been investigated and are still unknown. In this study, we examined whether dietary protein level, fatty acid type, namely saturated fatty acid and polyunsaturated fatty acid, and their interaction affect serum quinolinic acid concentration in rats. Male Sprague-Dawley rats (4-weeks old) were fed with 20% casein + 10% stearic acid diet (20C10S), 20% casein + 10% linoleic acid diet (20C10L), 40% casein + 10% stearic acid diet (40C10S), or 40% casein + 10% linoleic acid diet (40C10L) for 8 days, and serum quinolinic acid concentration and ACMSD activity were determined. Serum quinolinic acid concentration was significantly increased in the 40C10L group compared with other three groups. There was also the negative correlation between the sum of liver and kidney ACMSD activities, and serum quinolinic acid concentration per tryptophan intake (r = 0.8209, p < 0.01). Increased serum QA concentrations are probably due to a decreased ACMSD activity.

Topics: Analysis of Variance; Animals; Body Weight; Carboxy-Lyases; Caseins; Diet; Dietary Proteins; Dose-Response Relationship, Drug; Fatty Acids; Kidney; Linoleic Acid; Liver; Male; Organ Size; Quinolinic Acid; Rats; Rats, Sprague-Dawley; Stearic Acids; Tryptophan

Corticosteroid therapy for Duchenne muscular dystrophy is effective but associated with long-term side effects. To determine the potential therapeutic benefit from four nutritional compounds (creatine monohydrate, conjugated linoleic acid, alpha-lipoic acid, and beta-hydroxy-beta-methylbutyrate) alone, in combination, and with corticosteroids (prednisolone), we evaluated the effects on several variables in exercising mdx mice. Outcome measures included grip strength, rotarod performance, serum creatine kinase levels, muscle metabolites, internalized myonuclei, and retroperitoneal fat pad weight. In isolation, each nutritional treatment showed some benefit, with the combination therapy showing the most consistent benefits. Prednisolone and the combination therapy together provided the most consistent evidence of efficacy; increased peak grip strength (P < 0.05), decreased grip strength fatigue (P < 0.05), decreased number of internalized myonuclei (P < 0.01), and smaller retroperitoneal fat pad stores (P < 0.001). This study provided evidence for therapeutic benefit from a four-compound combination therapy alone, and in conjunction with corticosteroids in the mdx model of DMD.

Topics: Animals; Body Weight; Creatine Kinase; Creatinine; Dietary Supplements; Linoleic Acid; Mice; Mice, Inbred mdx; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Physical Fitness; Prednisolone; Rotarod Performance Test; Thioctic Acid; Treatment Outcome; Valerates

The purpose of this study was to determine whether the dose of (n-3) fatty acids (FA) administered, independent of the relative ratio of (n-6) to (n-3) FA in the food, influences plasma FA composition in dogs. Healthy female, geriatric beagles (7-10 y old) were fed foods containing (n-6) to (n-3) FA ratios of either 40.0:1 or 1.4:1 for 12 wk (study 1) or 36 wk (study 2). In study 3, beagles were fed food with the same 1:1 ratio of (n-6) to (n-3) FA, but with increasing concentrations of (n-6) and (n-3) FA. Plasma FA concentrations were measured after completing the feeding studies. In studies 1 and 2, dogs fed fish oil-enriched food with a high (n-3) FA concentration had higher plasma total (n-3) FA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) concentrations and lower plasma total (n-6) FA, linoleic acid, and arachidonic acid concentrations than dogs fed corn oil-enriched food with a low (n-3) FA concentration (P < 0.001). Both inclusion of fish oil (P < 0.001) and increased food intake independent of treatment effects increased the plasma DHA (P = 0.05) concentration. Furthermore, constancy of the dose of (n-3) FA administered over long periods of time was necessary to maintain plasma levels of total (n-3) FA, EPA, and DHA. In study 3, up to certain dietary concentrations (6.3 g total (n-3) FA/kg food for DHA and 9.8 g total (n-3) FA/kg food for EPA), the dose of (n-3) FA administered, independent of the (n-6) to (n-3) FA ratio, determined the plasma (n-3) FA composition. Results from our studies indicate that approximately 175 mg DHA/(kg body weight . d) is required to attain maximum plasma levels of DHA.

Topics: Animals; Arachidonic Acid; Body Weight; Corn Oil; Diet; Docosahexaenoic Acids; Dogs; Dose-Response Relationship, Drug; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Fish Oils; Food, Fortified; Linoleic Acid

Taste is intimately associated with food choice, yet little is known about the role of taste in preferences for dietary fat, a major component of many foods. We measured the taste threshold for linoleic acid (LA), an essential free fatty acid found in dietary fat, before and after bilateral transections of the chorda tympani nerve (CTX) in adult male and female rats. We conditioned a taste aversion to 88 microM LA and assessed the generalization of the aversion to lower LA concentrations to determine LA discrimination thresholds. We discovered that female rats had a lower LA discrimination threshold (approximately 2.75 microM LA) than did male rats (approximately 11 microM LA). In another set of animals, we performed CTX and found that CTX elevated LA threshold to the same level (approximately 22 microM LA) in male and female rats. Finally, we evaluated licking responses to 11, 22, 44 and 88 microM LA mixed in sucrose by male rats and ovariectomized (OVX) female rats treated with estradiol benzoate or oil vehicle. All rats increased licking to increasing LA concentrations, but OVX rats responded to a lower LA concentration (22 microM) than did males (44 microM) in 10-s trials. However, estradiol did not affect this outcome. Collectively, these experiments show that male and female rats use taste to discriminate LA and that the chorda tympani nerve, which innervates taste buds on the anterior tongue, plays a role in this discrimination. Furthermore, sex differences in fat preferences may depend on differences in fatty acid taste thresholds as well as on the taste stimuli with which fat is combined.

Topics: Analysis of Variance; Animals; Behavior, Animal; Body Weight; Central Nervous System Depressants; Chorda Tympani Nerve; Discrimination, Psychological; Dose-Response Relationship, Drug; Drinking Behavior; Drug Interactions; Ethanol; Facial Nerve Diseases; Female; Food Preferences; Linoleic Acid; Male; Ovariectomy; Rats; Rats, Sprague-Dawley; Sex Factors; Sucrose; Sweetening Agents; Taste; Taste Threshold

Conjugated linoleic acids (CLA) affect atherogenesis, but mechanisms are not well understood. We explored how two isomers of CLA, cis9, trans11-CLA and trans10, cis12-CLA, affected lipid and glucose metabolism, as well as hepatic protein expression, in apolipoprotein E knockout mice. After 12 wk of intervention, plasma triglyceride, NEFA, and glucose concentrations were significantly higher in the trans10, cis12-CLA group, whereas plasma triglyceride, NEFA, glucose, and insulin concentrations were significantly lower in the cis9, trans11-CLA group, compared with control mice consuming linoleic acid. Proteomics identified significant up- or down-regulation of 113 liver cytosolic proteins by either CLA isomer. Principal component analysis revealed that the treatment effect of cis9, trans11-CLA was mainly explained by the up-regulation of different posttranslational forms of heat shock protein 70 kD. In contrast, the treatment effect of trans10, cis12-CLA was mainly explained by up-regulation of key enzymes in the gluconeogenic, beta-oxidation, and ketogenesic pathways. Correlation analysis again emphasized the divergent effects of both CLA isomers on different pathways, but also revealed a linkage between insulin resistance and increased levels of hepatic serotransferrin. Thus, our systems biology approach provided novel insights into the mechanisms by which individual CLA isomers differentially affect pathways related to atherogenesis, such as insulin resistance and inflammation.

Topics: Animal Feed; Animals; Apolipoproteins E; Atherosclerosis; Blood Glucose; Blotting, Western; Body Composition; Body Weight; Cytosol; Diet; Fatty Acids; Genetic Linkage; Glucose; HSP70 Heat-Shock Proteins; Inflammation; Insulin; Insulin Resistance; Linoleic Acid; Linoleic Acids, Conjugated; Liver; Male; Mice; Mice, Knockout; Oxygen; Perfusion; Principal Component Analysis; Proteomics; Systems Biology; Triglycerides

The objective was to evaluate the effects of feeding ground canola seed on the fatty acid profile, yield, and composition of milk from dairy cows. Twenty-four multiparous Holstein cows (548.3 +/- 11.9 kg body weight and 28 +/- 9 d in lactation) were randomly assigned to 1 of 2 treatments: Control (CON) or ground canola seed treatment (GCS) with 14% [of diet dry matter (DM)] of the total ration as ground canola seed containing 34% lipid. Diets contained 20% crude protein, but varied in net energy as a result of fat content differences of 2.5% and 6.4% (DM) for CON and GCS, respectively. Diets were composed of corn, corn silage, alfalfa (50:50 ground hay and haylage, DM basis), soybean and blood meal, and vitamins and minerals. Mechanically extruded canola meal was used in the CON diet to adjust for the protein from canola seed in the GCS diet. Cows were housed in tie-stalls and fed and milked twice daily for 10 wk. The inclusion of ground canola seed did not alter DM intake, weight gain, or body condition score of cows. Milk fat from GCS cows had greater proportions of long-chain fatty acids (> or = 18 carbons) and a lower ratio of n-6 to n-3 fatty acids. Feeding GCS reduced the proportion of short- and medium-chain fatty acids. Milk fat from cows fed GCS had a greater proportion of vaccenic acid and tended to have a higher proportion of cis-9,trans-11 conjugated linoleic acid. Actual and 3.5% fat-corrected milk yields were similar between treatments. The milk fat and protein percentages were lower for GCS cows, but total yield of these components was similar between treatments. Milk urea nitrogen was lower and serum urea nitrogen tended to be lower in cows fed canola seed. Serum glucose, insulin, and nonesterified fatty acids were not altered, but serum triglycerides were higher in GCS cows. Ammonia and total volatile fatty acids tended to be lower in ruminal fluid from GCS cows; rumen pH was unchanged. Feeding canola seed to lactating dairy cows resulted in milk fat with higher proportions of healthful fatty acids without affecting milk yield or composition of milk.

Topics: Animal Feed; Animals; Blood Glucose; Body Weight; Brassica rapa; Cattle; Diet; Dietary Fats; Dietary Proteins; Fats; Fatty Acids; Fatty Acids, Nonesterified; Fatty Acids, Volatile; Female; Fermentation; Hydrogen-Ion Concentration; Insulin; Lactation; Linoleic Acid; Linoleic Acids, Conjugated; Milk; Rumen

The activity of a single IP administration (15 or 30 mg/Kg body weight) of vanillyl nonanoate, a simplified analog of capsiate, on ferric nitrilotriacetate (Fe-NTA)-mediated oxidative damage was investigated. A sub-lethal dose of Fe-NTA (15 mg Fe/Kg body weight) was administered IP to rats; animals were sacrificed, and kidney and plasma were collected 1 h after injection. In response to the Fe-NTA administration, a reduction of the levels of total lipids, total unsaturated fatty acids and cholesterol was observed, accompanied by a rise in the concentrations of malondialdehyde (MDA), conjugated dienes fatty acids hydroperoxides and 7-ketocholesterol in plasma and kidney 1 h after administration. A pre-treatment with synthetic capsiate (SCPT) showed remarkable protective effect on the reduction of the levels of total lipids, total unsaturated fatty acids and cholesterol, and the cellular antioxidant vitamin E, inhibiting the increase of MDA, conjugated dienes fatty acids hydroperoxides and 7-ketocholesterol in the plasma and kidney. The protective effect of SCPT and two analogues (vanillyl alcohol and vanillin) during the linoleic acid and cholesterol oxidation was investigated in in vitro systems, providing evidence of definite structure-activity relationships.

Topics: Analysis of Variance; Animals; Antioxidants; Body Weight; Capsaicin; Cholesterol; Chromatography, High Pressure Liquid; Fatty Acids; Ferric Compounds; Hydrogen Peroxide; Ketocholesterols; Kidney; Linoleic Acid; Lipid Peroxidation; Lipids; Malondialdehyde; Models, Chemical; Models, Statistical; Mutagens; Nitrilotriacetic Acid; Oxidative Stress; Oxygen; Rats; Rats, Wistar; Structure-Activity Relationship; Time Factors; Vanillic Acid

The interaction of dietary protein type and fat level on the body fat-reducing activity of conjugated linoleic acid (CLA) was studied in male rats fed diets containing casein (CAS) or soy protein (SOY) as a protein source with low fat (LF, 6.0% soybean oil) or high fat (HF, 13.0% soybean oil) combinations for 4 weeks. CLA was added at the 1.0% level to all diets. The weight of perirenal adipose tissue tended to be lower in the SOY groups than in the corresponding CAS groups, and the difference between the LF diets was significant. The weight of epididymal adipose tissue showed a similar but insignificant trend. The weight of brown adipose tissue was heaviest on the SOY-HF diet and lowest on two CAS diets, the SOY-LF diet being intermediate. The concentration of serum leptin was lowest on the SOY-LF diet and was significantly lower than that of the corresponding CAS group, but this difference disappeared when the dietary fat level increased. The serum cholesterol-lowering activity of SOY in relation to CAS was reproduced even when CLA was given. Thus the body fat-reducing activity of CLA was most marked when rats were fed the SOY-LF diet. Although the CAS-HF diet increased body fat deposition, the magnitude of the reduction by lowering dietary fat level was more marked than in the case of SOY. These results indicate a complicated interaction of dietary manipulations with the body fat-reducing effect of CLA, but the combination of CLA with the SOY-LF diet appears to be an appropriate approach.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Body Weight; Caseins; Cytokines; Diet; Dietary Fats; Dietary Proteins; Epididymis; Fatty Acids; Leptin; Linoleic Acid; Lipid Metabolism; Lipids; Liver; Male; Organ Size; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Soybean Proteins; Weight Gain

N-3 polyunsaturated fatty acids and estrogens are recognized as protective factors of atherosclerosis, however their interactions on cholesterol metabolism remain unclear. Male and female hamsters were fed for 9 weeks diets containing 12.5% lipids and rich in either alpha-linolenic acid ("linseed" diet) or saturated fatty acids ("butter" diet). Hamsters fed the "linseed" diet exhibited lower plasma concentrations of cholesterol (-29%), total LDL (-35%) and HDL (-17%), glucose (-20%), insulin (-40%) and of the LDL-cholesterol/HDL-cholesterol ratio (-27%) than those fed the "butter" diet. In the liver, cholesterol content was 2.7-fold lower in response to the "linseed" diet, whereas the concentration of HDL receptor (SR-BI) and the activities of HMGCoA reductase and cholesterol 7alpha-hydroxylase were 30 to 50% higher than with the "butter" diet. By contrast, the LDL receptor concentration did not vary with the diet. Females exhibited higher concentration of LDL (+24%), lower concentration of plasma triglycerides (-34%), total VLDL (-46%) and VLDL-cholesterol (-37%) and of biliary phospholipids (-19%). Besides, there was also an interaction between gender and diet: in males fed the "butter" diet, plasma triglycerides and VLDL concentration, were 2 to 4 fold higher than in the other groups. These data suggest that gene and/or metabolic regulations by fatty acids could interact with that of sex hormones and explain why males are more sensitive to dietary fatty acids.

Topics: Administration, Oral; Animals; Bile; Body Weight; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cricetinae; Diet; Dietary Fats; Female; Linoleic Acid; Lipid Metabolism; Liver; Male; Mesocricetus; Organ Size; Receptors, LDL; Sex Characteristics

The trans-10,cis-12 isomer of conjugated linoleic acid (CLA) reduces body fat gain in animals and inhibits stearoyl-CoA desaturase (SCD) activity in 3T3-L1 adipocytes. To test whether CLA's body fat reduction is mediated by SCD1, wild-type and SCD1-null mice were fed diet supplemented with 0.2% trans-10,cis-12 (t10c12) CLA for 4 weeks. The t10c12 CLA-supplemented diet significantly reduced body fat mass in both wild type and SCD1-null mice. Similarly, t10c12 CLA diet decreased blood triglyceride and free fatty acid levels regardless of SCD1 genotypes. Mice fed t10c12 CLA exhibited increased mRNA expression of fatty acid synthase and uncoupling protein 2 in both genotypes. Taken together, the effects of t10c12 CLA on reduction of body fat gain, blood parameters, and mRNA expression in both SCD1-null mice and wild-type mice were similar, indicating that the anti-obesity effect of t10c12 CLA may be independent of the effects of this CLA isomer on SCD1 gene expression and enzyme activity.

Topics: 3-Hydroxybutyric Acid; Adipose Tissue; Animal Feed; Animals; Anti-Obesity Agents; Blood Glucose; Body Weight; Cholesterol; Fats; Fatty Acids; Gene Expression; Linoleic Acid; Liver; Male; Mice; Mice, Knockout; Muscles; RNA, Messenger; Stearoyl-CoA Desaturase; Triglycerides

To determine the effect of a short-term isocaloric exchange of alpha-linolenic acid (ALA, 18:3n3) for linoleic acid (LA, 18:2n6) on fasting levels of soluble interleukin-6 receptor (sIL6R), and soluble tumor necrosis factor-alpha receptors 1 and 2 (sTNFR1 and sTNFR2) in healthy normal weight and overweight/obese adult males.. Four-day clinical intervention study with 0.5% or 5% of total energy from ALA. Fasting (10 h) blood samples were obtained on the morning of day 5 in both diet treatments to measure sTNFR1, sTNFR2, and sIL6R.. Nine normal weight (BMI < 25 kg/m2) and seven overweight (BMI > or = 25 kg/m2) healthy males.. Fasting sIL6R decreased significantly from the control (C) diet following four days on the high ALA isocaloric (ISO) diet in normal weight and overweight/obese subjects (normal weight: C = 34.89 +/- 3.17 ng/ml, ISO = 30.91 +/- 2.24 ng/ml, p < 0.05; overweight/obese: C = 38.19 +/- 3.92 ng/ml, ISO = 33.57 +/- 2.47 ng/ml, p , 0.05). The dietary intervention did not have a significant effect on fasting sTNFR1 or sTNFR2.. The results suggest that an isocaloric exchange of ALA for LA can reduce fasting sIL6R concentration by approximately 11% after a four-day dietary intervention in both overweight/obese and normal weight subjects. The data also suggest that longer exposure to a similar diet may have the potential to reduce inflammatory burden and thus lower the risk of both cardiovascular disease as well as diabetes.

Topics: Adult; alpha-Linolenic Acid; Body Mass Index; Body Weight; Humans; Interleukin-6; Linoleic Acid; Male; Middle Aged; Receptors, Interleukin-6; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II

A study was conducted to elucidate hormonal control of ketogenesis and glycogen deposition in primary cultures of porcine hepatocytes. Hepatocytes were isolated from pigs (54-68 kg) by collagenase perfusion and seeded into collagen-coated T-25 flasks. Monolayers were established in medium containing fetal bovine serum for 1 day and switched to a serum-free medium for the remainder of the culture period. Hepatocytes were maintained in DMEM/M199 containing 1% DMSO, dexamethasone (10(-6) or 10(-7) M), linoleic acid (3.4 x 10(-5) M), and carnitine (10(-3) M) for 3 days. On the first day of serum-free culture, insulin was added at 1 or 100 ng/ml and glucagon was added at 0, 1, or 100 ng/ml. Recombinant human leptin (200 ng/ml) was added during the final 24 h; medium and all cells were harvested on the third day. Concentrations of acetoacetate and beta-hydroxybutyrate (ketone bodies) in media and glycogen deposition in the cellular compartment were determined. Ketogenesis was highly stimulated by glucagon (1 and 100 ng/ml) and inhibited by insulin. In contrast, glycogen deposition was stimulated by insulin and attenuated by glucagon; high insulin was also associated with a reduction in the ketone body ratio (acetoacetate:beta-hydroxybutyrate). High levels of dexamethasone stimulated ketogenesis, but inhibited glycogen deposition at low insulin. Culture of cells with leptin for 24 h, over the range of insulin, glucagon, and dexamethasone concentrations had no effect on either glycogen deposition or ketogenesis. These data suggest that while adult porcine hepatocytes are indeed sensitive to hormonal manipulation, leptin has no direct influence on hepatic energy metabolism in swine.

Topics: Animals; Body Weight; Carnitine; Cells, Cultured; Culture Media, Serum-Free; Dexamethasone; Glucagon; Glucocorticoids; Glycogen; Hepatocytes; Humans; Insulin; Ketone Bodies; Leptin; Linoleic Acid; Recombinant Proteins; Swine

Alpha-linolenic acid (18:3omega3) has many important physiological functions including being beta-oxidized, serving a precursor to the synthesis of other lipids and it has immunomodulation properties. The objective of the present study was to test the effects of immunization and dietary 18:3omega3 on immune function and the fatty acid profile of immunized pig tissues. Piglets suckled from sows consuming either a control or high 18:3omega3 diet until 14 days old when they were weaned onto a similar diet as the sow and were moved to a segregated nursery for the remainder of the study. At 35 days of age, pigs on both diets (2 x 2 factorial design) received either an injection containing hen eggwhite lysozyme (HEWL), killed Mycobacterium tuberculosis and Freund's complete adjuvant (immunized) or phosphate buffered saline (PBS) (non-immunized) into the neck followed by a booster injection 2 weeks later and induction of delayed-type hypersensitivity (DTH) one week later. Immunization increased (compared to non-immunized) while the high 18:3omega3 diet decreased haptoglobin by 30% compared to pigs consuming the control diet. Immunized pigs had a seven-fold increase in antibodies to HEWL and pigs consuming the high 18:3omega3 diet also had transiently higher levels of serum antibodies. There was a diet by immunization interaction on the DTH reaction such that immunized pigs consuming the high 18:3omega3 had the largest DTH reaction. The neck muscle proximal to the site of injection of immunized pigs had 10-30% lower levels of triglyceride and phospholipid linoleic (18:2omega6) and 18:3omega3 compared to non-immunized pigs. Thus, a high 18:3omega3 intake in pigs modulates immune function and tissue fatty acids in response to immunization.

Topics: Adjuvants, Immunologic; alpha-Linolenic Acid; Animals; Antibodies; Antibody Formation; Antigens; Bacterial Proteins; Body Weight; Egg Proteins; Fatty Acids; Female; Immunity, Cellular; Linoleic Acid; Pregnancy; Swine; Tissue Extracts

We studied the effects of five high-fat semi-purified diets varying at a 4% (w/w) level in either stearic, oleic, linoleic, alpha-linolenic, or gamma-linolenic acid on body fat and energy metabolism in BALB/c mice. A diet containing caprylic, capric, lauric, and myristic acid was used as a reference diet and a diet with 4% conjugated linoleic acid (CLA) was used as a positive control as it is known to effectively lower body fat in mice. The diets were fed for 35 d. Body fat was significantly lower in the CLA group than in the other groups but was not significantly different among the non-CLA groups. Among the non-CLA groups, the linoleic acid group tended to have the highest and the alpha-linolenic acid group the lowest proportion of body fat. In energy-balance studies, the percentage of energy intake that was stored in the body was significantly lower in the CLA group compared with the other dietary groups. The percentage of energy intake eliminated in excreta was highest in the stearic acid group followed by the gamma-linolenic acid group. These results were reflected in apparent fat digestibility, which was lowest in the stearic acid group. The percentage of energy intake expended as heat was highest in the CLA-fed mice. The results of the present study suggest that body fat and energy accretion in mice fed diets containing different C18 fatty acids is by far the lowest with CLA and that linoleic acid produced the highest fat intake and energy accretion.

Topics: Adipose Tissue; alpha-Linolenic Acid; Animals; Body Composition; Body Weight; Dietary Fats; Energy Metabolism; Fatty Acids; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids, Conjugated; Male; Mice; Mice, Inbred BALB C; Oleic Acid; Stearic Acids

Arachidonic acid (AA), a precursor of prothrombotic eicosanoids, is potentially atherogenic, but epidemiologic data are scarce. We evaluated the hypothesis that increased AA in adipose tissue is associated with increased risk of nonfatal acute myocardial infarction (MI), and if so, whether this association is related to dietary or adipose tissue linoleic acid. We studied the association between AA and MI in 466 cases of a first nonfatal acute MI, matched on age, gender, and residence to 466 population controls. Fatty acids (FA) were assessed by GC in adipose tissue samples collected from all subjects. Odds ratios (OR) and 95% CI were calculated from multivariate conditional logistic regression models. Subjects in the highest quintile of adipose tissue AA (0.64% of total FA) had a higher risk of nonfatal acute MI than those in the lowest quintile (0.29% of total FA), after adjusting for potential confounders including (n-3) and trans FAs (OR = 1.94, 95% CI: 1.07, 3.53, P for trend = 0.026). Adipose tissue AA was not correlated with dietary AA (r = 0.07), linoleic acid (r = 0.04), or other dietary (n-6) FAs, or with adipose tissue linoleic acid (r = -0.07). These data suggest that the association between MI and adipose tissue AA is not related to dietary intake of (n-6) FAs including linoleic acid. Better understanding of the metabolic factors that increase AA in adipose tissue is urgently needed.

Topics: Adipose Tissue; Age Factors; Aged; Arachidonic Acid; Body Size; Body Weight; Chromatography, Gas; Costa Rica; Diabetes Mellitus; Diet; Dietary Fats, Unsaturated; Female; Humans; Hypertension; Linoleic Acid; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Risk Factors; Sex Factors

Hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD; formerly termed picolinic carboxylase) [EC4.1.1.45] plays a key role in regulating NAD biosynthesis and the generation of quinolinate (quinolinic acid) from tryptophan. Quinolinate is a potent endogenous excitotoxin of neuronal cells. We previously reported that ingestion of fatty acids by rats leads to a decrease in their hepatic ACMSD activity. However, the mechanism of this phenomenon is not clarified. We previously purified ACMSD and cloned cDNA encoding rat ACMSD. Therefore, in this study, we examined the differential effect of fatty acids on ACMSD mRNA expression by Northern blot. Moreover, we measured quinolinic acid concentration in rats fed on fatty acid. When diets containing 2% level of fatty acid were given to male Sprague-Dawley rats (4 weeks old) for 8 days, long-chain saturated fatty acids and oleic acid did not affect ACMSD mRNA expression in the liver. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) strongly suppressed the liver ACMSD mRNA expression. In rats fed with high linoleic acid diet for 8 days, serum quinolinic acid was significantly increased as compared with the rats fed on a fatty acid-free diet under the condition of the approximately same calorie ingestion. These results suggest that the transcription level of ACMSD is modulated by polyunsaturated fatty acids, and suppressive potency of ACMSD mRNA is n-3 fatty acid family>linoleic acid (n-6 fatty acid)>saturated fatty acid. Moreover, this study provides the information that a high polyunsaturated fatty acid diet affects the production of quinolinic acid in serum by suppressing the ACMSD activity.

Topics: Animals; Body Weight; Carboxy-Lyases; Dietary Fats; Eating; Energy Intake; Gene Expression; Linoleic Acid; Liver; Male; Organ Size; Quinolinic Acid; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stearic Acids; Time Factors; Tryptophan

Feeding mice conjugated linoleic acid (9 cis,11 trans/9 trans,11 cis-and 10 trans,12 cis-CLA in equal amounts) resulted in triacylglycerol accumulation in the liver. The objective of this study was to examine whether this steatosis is associated with changes in hepatic fatty acid synthesis and oxidation. Therefore, we measured the activities of key enzymes of fatty acid synthesis, i.e., acetyl-CoA carboxylase and fatty acid synthase and of fatty acid oxidation, i.e., 3-hydroxy-acyl-CoA dehydrogenase and citrate synthase in livers of mice fed a diet with 0.5% (w/w) CLA. CLA (a 1:1 mixture of the 10 trans, 12 cis and 9 cis, 11 trans isomers of octadecadenoic acid) was administered for 3 and 12 weeks with high-oleic sunflower oil fed as control. The proportion of body fat was significantly lower on the CLA than on the control diet and this effect was already significant after 3 weeks. The specific activites of 3-hydroxy-acyl-CoA dehydrogenase and citrate synthase were unaffected by CLA both after 3 and 12 weeks. The specific activity of fatty acid synthase was nonsignificantly raised (by 12%) after 3 weeks on the CLA diet but had increased significantly (by 34%) after 12 weeks of feeding. The specific activity of acetyl-CoA carboxylase had also increased both after 3 weeks (by 53%) and 12 weeks (by 23%) on the CLA diet, but this effect did not reach statistical significance. Due to CLA-induced hepatomegaly, the overall capacity for both fatty acid oxidation and synthesis-as evidenced by the total hepatic activities of 3-hydroxy-acyl-CoA dehydrogenase, citrate synthase, acetyl-CoA carboxylase, and fatty acid synthase-was significantly greater in the CLA-fed group after 12 weeks, although the overall capacity for fatty acid synthesis had increased more than that for fatty acid oxidation. Thus, this study indicates that prolonged, but not short-term, feeding mice with CLA increased hepatic fatty acid synthesis relative to oxidation, despite the decrease in body fat and the increase in liver weight seen earlier. It is concluded that the observed CLA-induced changes in hepatic fatty acid synthesis and oxidation are the result, rather than the cause, of the lowering of body fat.

Topics: Animals; Body Composition; Body Weight; Citrate (si)-Synthase; Fatty Acid Synthases; Fatty Acids; Feeding Behavior; Hepatomegaly; Linoleic Acid; Lipids; Liver; Mice; Mice, Inbred BALB C; Organ Size; Oxidation-Reduction; Up-Regulation

Epidemiologic and animal model studies suggest that consumption of soy isoflavones may be associated with reduced risk of prostate cancer (PC). In addition, animal model studies suggest that conjugated linoleic acid (CLA), a natural positional isomer of linoleic acid, inhibits tumor growth in various models, including models of PC.. Based on the above-mentioned data, the objective of the present study was to test the hypothesis that supplementation of the diet with combinations of isoflavone-rich soy protein isolate and CLA would act to inhibit the growth of androgen-independent R-3327-AT-1 rat prostate tumor cells inoculated ectopically into male Copenhagen rats.. The results of this study indicate that neither an isoflavone-rich soy protein isolate (SPI), nor CLA inhibit the in vivo growth and development of prostate tumor cells when administered in the diet either singly or in combination. Moreover, at the highest concentrations SPI and CLA (i.e., 20% SPI, 1% CLA), there was a statistically significant increase in tumors volume over controls. Administration of SPI at 10% in the diet also enhanced tumor growth, whereas at 5%, SPI exerted no measurable effect. CLA administration alone had no observable effects on AT-1 tumor growth.. These results, in an established rat model, suggest caution in using isoflavone-rich SPI in human studies involving advanced hormone-refractory prostate cancer until further investigation of these effects are completed.

Topics: Animals; Body Weight; Cell Division; Isoflavones; Linoleic Acid; Male; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Soybean Proteins; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Conjugated linoleic acid (CLA) reportedly exerts anticarcinogenic and antiatherosclerotic effects in animals. To test the hypothesis that the putative antiatherosclerotic effect of CLA might derive from an anti-inflammatory or antioxidant action on lipoprotein metabolism, an acute phase response (APR) was elicited in hamsters while varying dietary cholesterol and vitamin E intakes in two experiments. The effect of CLA intake (to 1%) was examined with 0% (Experiment 1, 7 wk) and 0 or 0.3% (Experiment 2, 12 wk) cholesterol, at which point APR was induced. In hamsters not fed dietary cholesterol (Experiment 1), CLA exaggerated the rise in plasma and LDL cholesterol observed during the APR. When CLA was fed concurrently with cholesterol (Experiment 2), plasma and liver cholesterol were reduced up to 40% independent of the APR. In addition, CLA decreased body weight gain and adipose reserves in Experiment 1, but not in Experiment 2. Because CLA failed to attenuate APR and was not influenced by vitamin E status, an antioxidant/anti-inflammatory role was not apparent. However, the reduced burden on liver and lipoprotein cholesterol induced by CLA during cholesterol feeding, suggests that CLA curtailed cholesterol absorption, whereas the rise during APR suggests that CLA exaggerated the impaired clearance of plasma cholesterol associated with acute inflammation.

Topics: Acute-Phase Reaction; Animals; Body Weight; Cholesterol; Cricetinae; Diet; Linoleic Acid; Lipids; Liver; Male; Mesocricetus

Segregated early weaning (SEW) into a cleaner nursery increases food intake and growth in pigs, presumably because of reduced immune stimulation compared with conventionally reared, nonsegregated pigs (NSW). The aim of the present study was to evaluate the oxidation of linoleic acid (18:2omega6) and alpha-linolenic acid (18:3omega3) in SEW and NSW pigs. Pigs consumed a control or high 18:3omega3 diet (omega6 PUFA/omega3 PUFA; 21.3 vs. 2.5, respectively) and were weaned at either 14 days old into a SEW nursery or at 21 days old into a conventional NSW nursery. The major acute-phase protein of pigs but not haptoglobin increased in 35-day-old NSW pigs. NSW pigs had 15-25% lower carcass 18:2omega6 and 20-30% lower carcass 18:3omega3 (% composition) at 49 days old. Between 35- and 49-days-old, NSW pigs had a higher whole-body oxidation of 18:2omega6 (40-120%) and 18:3omega3 (30-80%). The high 18:3omega3 diet decreased the whole-body oxidation of 18:2omega6 by 73% and of 18:3omega3 by 63% in NSW pigs. We conclude that moderately cleaner housing SEW significantly decreases 18:2omega6 and 18:3omega3 oxidation in pigs.

Topics: alpha-Linolenic Acid; Animals; Body Weight; Dietary Fats; Eating; Female; Linoleic Acid; Oxidation-Reduction; Pregnancy; Swine; Tissue Extracts; Weaning

We evaluated the effect of cis-9, trans-11 (9c,11t) and trans-10, cis-12 (10t,12c) conjugated linoleic acid (CLA) on the immune system in C57BL/6J mice. Mice were fed experimental diets containing 0% CLA (controls), 1% 9c,11t-CLA, 1% 10t,12c-CLA or a 1:1 mixture (0.5% + 0.5%) of these two CLA isomers for 3 wk. Relative spleen weights of all CLA fed mice were greater than the controls. Spleen lymphocytes isolated from the mice fed 10t,12c-CLA produced more immunoglobulin (Ig)A and IgM but not IgG when stimulated with concanavalin A (ConA) compared with controls. IgA production from unstimulated spleen lymphocytes was greater in the 10t, 12c-CLA group than in controls. Conversely, 9c,11t-CLA did not affect the production of any of the Ig subclasses. Lymphocytes isolated from 9c,11t-CLA fed mice produced more tumor necrosis factor-alpha than the control group. The proportion of B cells in the spleen lymphocyte population was significantly lower in the 9c,11t-CLA group, and higher in the 10t,12c-CLA group than in the controls. Compared with the control group, the percentage of CD4(+) T cells was lower in the 10t,12c-CLA group, and the percentage of CD8(+) T cells was higher in the 9c,11t-CLA group. Furthermore, the percentage of CD8(+) T cells was higher in the 1:1 mixture group than in controls. The CD4(+)/CD8(+) ratio was lower in the 1:1 mixture group than in controls. These results suggest that 9c,11t and 10t,12c-CLA can stimulate different immunological effects and that the simultaneous intake of the two isomers can change the T cell population.

Topics: Animals; B-Lymphocytes; Body Weight; CD4 Lymphocyte Count; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes; Cytokines; Diet; Eating; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Linoleic Acid; Lymphocyte Count; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Spleen; T-Lymphocytes

The fatty acid-conjugated linoleic acid (CLA) enhances glucose tolerance and insulin action on skeletal muscle glucose transport in rodent models of insulin resistance. However, no study has directly compared the metabolic effects of the two primary CLA isomers, cis-9,trans-11-CLA (c9,t11-CLA) and trans-10,cis-12-CLA (t10,c12-CLA). Therefore, we assessed the effects of a 50:50 mixture of these two CLA isomers (M-CLA) and of preparations enriched in either c9,t11-CLA (76% enriched) or t10,c12-CLA (90% enriched) on glucose tolerance and insulin-stimulated glucose transport in skeletal muscle of the insulin-resistant obese Zucker (fa/fa) rat. Animals were treated daily by gavage with either vehicle (corn oil), M-CLA, c9,t11-CLA, or t10,c12-CLA (all CLA treatments at 1.5 g total CLA/kg body wt) for 21 consecutive days. During an oral glucose tolerance test, glucose responses were reduced (P < 0.05) by 10 and 16%, respectively, in the M-CLA and t10,c12-CLA animals, respectively, whereas insulin responses were diminished by 21 and 19% in these same groups. There were no significant alterations in these responses in the c9,t11-CLA group. Insulin-mediated glucose transport activity was enhanced by M-CLA treatment in both type I soleus (32%) and type IIb epitrochlearis (58%) muscles and by 36 and 48%, respectively, with t10,c12-CLA. In the soleus, these increases were associated with decreases in protein carbonyls (index of oxidative stress, r = -0.616, P = 0.0038) and intramuscular triglycerides (r = -0.631, P = 0.0028). Treatment with c9,t11-CLA was without effect on these variables. These results suggest that the ability of CLA treatment to improve glucose tolerance and insulin-stimulated glucose transport activity in insulin-resistant skeletal muscle of the obese Zucker rat are associated with a reduction in oxidative stress and muscle lipid levels and can be specifically ascribed to the actions of the t10,c12 isomer. In the obese Zucker rat, the c9,t11 isomer of CLA is metabolically neutral.

Topics: Abdomen; Adipose Tissue; Animals; Biological Transport, Active; Body Weight; Fatty Acids, Nonesterified; Female; Glucose; Glucose Tolerance Test; Insulin; Isomerism; Linoleic Acid; Lipid Metabolism; Muscle Proteins; Muscle, Skeletal; Obesity; Organ Size; Oxidative Stress; Rats; Rats, Zucker

Conjugated linoleic acids (CLA) have recently been recognized to reduce body fat and plasma lipids in some animals. This study demonstrated that the steatosis accompanying the fat loss induced by trans-10,cis-12-C(18:2) (CLA2) and not cis-9,trans-11-C(18:2) (CLA1) isomer in C57BL/6j mice was not due to an alteration of the liver lipoprotein production that was even increased. The 3-fold decrease in plasma triacylglycerol contents and the induction of mRNA expression of low-density lipoprotein receptors concomitantly observed in CLA2-fed mice suggested an increase in the lipoprotein clearance at the level of the liver itself. CLA1 feeding produced similar but attenuated effects on triglyceridaemia only.

Topics: Animals; Base Sequence; Body Weight; DNA Primers; Esterification; Fatty Acids; Fatty Liver; Linoleic Acid; Lipoproteins, VLDL; Liver; Mice; Mice, Inbred C57BL; Myocardium; RNA, Messenger; Triglycerides

The effect of polyunsaturated fatty acids (PUFA), in particular conjugated linoleic acid (CLA), on Ca and bone metabolism is unclear. In a 2x2 factorial design study, forty male 4-week-old rats were fed a control diet containing 70 g added fat (soyabean oil (SBO; n-6 PUFA-rich diet) or menhaden oil-safflower oil (MSO; n-3 PUFA-rich diet))/kg diet with 0 or 10 g CLA/kg for 8 weeks. Ex vivo prostaglandin E2 biosynthesis by bone organ culture was significantly higher (P<0.001) in rats consuming SBO compared with MSO, irrespective of CLA. Addition of the CLA treatment to either diet further lowered (P<0.05) ex vivo prostaglandin E2 production. Neither PUFA type nor CLA altered circulating or femoral mRNA levels of osteocalcin (a marker of bone formation) or insulin-like growth factor-I (a mediator of bone metabolism). While urinary pyridinium crosslinks levels (markers of bone resorption) were unaffected by CLA irrespective of PUFA type, they were significantly higher (P<0.05) in rats consuming SBO compared with MSO irrespective of CLA. Net fractional (%) and absolute (mg) Ca absorption were significantly (P<0.01 and P<0.05 respectively) higher in CLA-supplemented than unsupplemented animals fed on the n-3 PUFA-rich diet, whereas CLA had no effect in animals fed the n-6 PUFA-rich diet. There was no effect of CLA supplementation on bone mineral mass. In conclusion, CLA supplementation over 8 weeks appeared to enhance Ca absorption in young growing rats fed an n-3 PUFA-rich diet, but had no measurable effect on bone metabolism or bone mass over this time frame.

Topics: Absorption; Animals; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Calcium; Dietary Supplements; Dinoprostone; Fatty Acids, Unsaturated; Insulin-Like Growth Factor I; Linoleic Acid; Male; Osteocalcin; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction

The objective of this study was to compare the effects of conjugated linoleic acid (CLA) as triacylglycerols (TAG) or free fatty acids (FFA) on body composition and energy balance in mice. We fed four groups of 5-wk-old Balb-C mice (n = 9) semipurified diets containing either CLA (0.5 g CLA/100 g of diet) or high oleic sunflower oil (HOSF) in the form of FFA or TAG for 42 d. Body composition was determined and the energy in the carcasses, excreta and food was measured in a bomb calorimeter. The amount of body fat was 4.72 +/- 0.95 g (17.9 +/- 2.8%) in the HOSF-FFA group, 2.36 +/- 0.29 g (9.4 +/- 1.0%) in the CLA-FFA mice (mean +/- SD, P < 0.05), 4.76 +/- 0.74 g (18.2 +/- 2.2%) in the HOSF-TAG group and 2.32 +/- 0.38 g (9.3 +/- 1.1%) in the CLA-TAG mice (P < 0.05). The percentage of energy intake that was stored in the body was 3.5 +/- 1.2% in the HOSF-FFA group, 0.6 +/- 0.3% in the CLA-FFA group (P < 0.05), 3.5 +/- 1.1% in the HOSF-TAG group and 0.5 +/- 0.4 in the CLA-TAG mice (P < 0.05). Conversely, the percentage of energy intake that was expended as heat was 89.4 +/- 1.2% in the HOSF-FFA group, 92.4 +/- 0.8% in the CLA-FFA mice (P < 0.05), 89.47 +/- 1.23% in the HOSF-TAG group and 92.2 +/- 0.4% in the CLA-TAG group (P < 0.05). Thus, CLA in the form of FFA or TAG had similar effects on body composition and energy balance.

Topics: Animals; Blood Glucose; Body Composition; Body Weight; Dietary Fats; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Linoleic Acid; Lipids; Male; Mice; Mice, Inbred BALB C; Oleic Acid; Plant Oils; Sunflower Oil; Triglycerides

Conjugated linoleic acid (CLA) is the term given to a group of positional and geometric isomers of the essential fatty acid linoleic acid. CLA is found naturally in foods such as dairy and meat products. CLA is reported to have a number of beneficial effects including anticarcinogenic activity. However, safety data are limited. Clarinol G80 is a commercial preparation containing equal amounts of the 9cis,11trans and 10trans,12cis CLA isomers in the form of glycerides. In order to support the safety-in-use of Clarinol G80 as an ingredient in food, the preparation was tested in two in vitro mutagenicity assays, an Ames test and an in vitro cytogenetics assay, and a 90-day repeat-dose oral toxicity rat study. Clarinol G80 was non-mutagenic in both in vitro assays. In the 90-day study, Clarinol G80 produced hepatocellular hypertrophy in female rats at the highest dose level (15% w/w). This effect was an adaptive effect in response to feeding high levels of Clarinol G80 in the diet and was reversible upon withdrawal of test material. An increase in plasma insulin levels was also observed female rats fed 15% w/w Clarinol G80 but there was no effect on plasma glucose levels. A No Observed Adverse Effect Level of 2433 mg/kg bw/day for male and 2728 mg/kg bw/day female rats was identified in the study.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Behavior, Animal; Blood Glucose; Body Weight; Chromosome Aberrations; Diet; Drinking; Eating; Eye; Isomerism; Linoleic Acid; Lymphocytes; Mutagenicity Tests; Mutagens; Organ Size; Rats; Safflower Oil; Salmonella typhimurium

Cyclic FA monomers (CFAM) formed during heating of alpha-linolenic acid have been reported to interfere in hepatic metabolism in a putatively peroxisome proliferator-activated receptor alpha (PPARalpha)-dependent manner. In the present work, CFAM (0.5% of the diet) were administered for 3 wk to wild-type and PPARalpha-null mice of both genders to elucidate the role of PPARalpha in mediating the effects of CFAM on the activity of acyl-CoA oxidase (ACO) and omega-laurate hydroxylase (CYP4A), the regulation of which is known to be dependent on the PPARalpha. Dietary CFAM enhanced CYP4A activity threefold in male and female wild-type mice. This effect was abolished in PPARalpha-null mice. A twofold induction of ACO activity was found in wild-type female mice fed CFAM; however, no effect was seen in males. In wild-type animals, (omega-1)-laurate hydroxylase (CYP2E1) activity, the expression of which has not been shown to be PPARalpha dependent, was not affected by the CFAM diet. In contrast, stearoyl-CoA desaturase activity was reduced in wild-type mice. CFAM feeding reduced the activities of ACO, CYP2E1, and stearoyl-CoA desaturase and caused accumulation of lipids in the livers of female PPARalpha-null mice. These data show that CFAM apparently activate gene expression via the PPARalpha and have profound effects on lipid homeostasis, exacerbating the disturbances preexisting in mice lacking functional PPARalpha. Although the data emphasize the importance of PPARalpha in the metabolism of the CFAM, these results show that PPARalpha is not the exclusive mediator of the effects of CFAM in lipid metabolism in mice.

Topics: Animal Feed; Animals; Body Weight; Cyclization; Cytochrome P-450 CYP4A; Diet; Fatty Acids; Female; Gene Deletion; Linoleic Acid; Liver; Male; Mice; Mice, Knockout; Molecular Structure; Oxidoreductases; Receptors, Cytoplasmic and Nuclear; Stearoyl-CoA Desaturase; Transcription Factors

Cis 9, trans 11 (c 9, t11)-18:2 and trans 10, cis 12 (t10, c12)-18:2 are the major conjugated linoleic acid (CLA) isomers in dietary supplements which reduce milk fat content in nursing women. The present study evaluated the effects of each CLA isomer or vaccenic acid on body composition and tissue fatty acids during lactation in mice. Dams were fed 30 g rapeseed oil (control)/kg diet or 20 g control plus 10 g 18:0, trans 11-18:1 (t11-18:1), c 9, t11-18:2, or t10, c12-18:2. Dietary t10, c12-18:2 reduced food intake by 18 % and carcass fat weight of the dams by 49 % compared with the other treatments. Milk fat percentage ranked by treatment was 18:0>t11-18:1=c 9, t11-18:2>t10, c12-18:2. The sum of saturated 12:0 to 16:0 in milk fat was lower when c 9, t11-18:2 was fed compared with the control, 18:0, or t11-18:1 treatments. Dietary t10, c12-18:2 caused further reductions in milk fat 12:0 to 16:0. The proportion of CLA isomers was 3-fold greater in milk fat than in the carcasses of the dams. The pups nursing from the dams fed t10, c12-18:2 had the lowest body weights and carcass fat, protein, and ash contents. Nursing from the dams fed c 9, t11-18:2 also resulted in lower carcass fat compared with the 18:0 or t11-18:1 treatments. The ratios of cis 9-16:1:16:0 or cis 9-18:1:18:0, proxies for Delta(9)-desaturase activity, were markedly lower in the carcasses of the dams and pups fed t10, c12-18:2. The ratio of 20:4n-6:18 : 2n-6, a proxy for Delta(6)- and Delta(5)-desaturase and elongase activity, in the liver of the dams and pups fed t10, c12-18:2 also was lower. Dietary t11-18:1 enhanced the content of c 9, t11-18:2 in milk fat and carcasses. As in previous studies, the reduction in food intake by t10, c12-18:2 could not entirely account for the marked decrease in carcass fat content and milk fat concentration. T10, c12-18:2 probably had a negative effect on Delta(9)-desaturase and mammary de novo fatty acid synthesis. Although these effects need to be confirmed in lactating women, the results suggest that the consumption of supplements containing t10, c12-18:2 should be avoided during the nursing period.

Topics: Animals; Animals, Suckling; Blood Glucose; Body Composition; Body Weight; Dietary Supplements; Eating; Fatty Acids; Female; Growth; Lactation; Linoleic Acid; Lipids; Liver; Mice; Mice, Inbred Strains; Milk; Oleic Acids

Linoleic (18:2n-6) and alpha-linolenic acids (18:3n-3) have many important physiological functions including immunomodulation. We tested how immunization influences the metabolism of 18:2n-6 and 18:3n-3 in the neck muscle of pigs. At 35 d old, pigs received either an intramuscular neck injection containing hen egg white lysozyme (HEWL), killed Mycobacterium tuberculosis, and Freund's complete adjuvant (immunized) or PBS (control). At 49 d old, immunized pigs received a booster injection of HEWL and Freund's incomplete adjuvant, and the control pigs received PBS into the neck. At 56 d old, all pigs received an intradermal injection of Mycobacterium bovis into the hind leg to induce a delayed-type hypersensitivity (DTH) reaction. At 57 d old, immunized pigs had a twofold increase in serum haptoglobin, a 10-fold increase in antibodies to HEWL, and the skinfold at the DTH reaction site was 10 times thicker than the controls. Both 18:2n-6 and 18:3n-3 (% composition) were approximately 25% lower in muscle TG, 40% lower in FFA, 50% lower in phospholipids, but not different in cholesteryl esters of the neck muscle of immunized pigs. The antigens in this model induce an increased response in the innate (haptoglobin), humoral (antibodies), and cellular (DTH) immune systems as well as a preferential decrease of 18:2n-6 and 18:3n-3 in the inflamed neck muscle. It appears that 18:2n-6 and 18:3n-3 are preferentially metabolized (possibly beta-oxidized) in response to antigens.

Topics: alpha-Linolenic Acid; Animals; Antigens; Body Weight; Cholesterol Esters; Fatty Acids; Freund's Adjuvant; Hypersensitivity, Delayed; Injections, Intramuscular; Linoleic Acid; Neck Muscles; Phospholipids; Swine; Time Factors; Triglycerides

In diabetes there is a decrease in membrane arachidonic (AA) and docosahexaenoic (DHA) acids and a concomitant increase in linoleic (LA) and alpha-linolenic (ALA) acids. This metabolic perturbation is thought to be due to impaired activity of Delta(6)- and Delta(5)-desaturases. Triacylglycerols are the major lipid pool in plasma and liver tissue and have a significant influence on fatty acid composition of membrane and circulating phospholipids. Data on the distribution of n-6 and n-3 polyunsaturated fatty acids of triacylglycerols in diabetes are sparse. We investigated whether streptozotocin-induced diabetes in Sprague-Dawley rats alters fatty acid composition of triacylglycerols and free fatty acids of liver tissue. The animals were fed a breeding diet prior to mating, during pregnancy and lactation. On days 1-2 of pregnancy, diabetes was induced in 10 of the 25 rats. Liver was obtained at post partum day 16 for analysis. Relative levels of LA (P=0.03), dihomo-gamma-linolenic acid (DHGLA) (P=0.02), AA (P=0.049), total n-6 (P=0.02), ALA (P=0.013), eicosapentaenoic acid (EPA) (P=0.004), docosapentaenoic acid (22:5n-3, DPA) (P=0.013), DHA (P=0.033), n-3 metabolites (P=0.015) and total n-3 (P=0.011) were significantly higher in the triacylglycerols of the diabetics compared with the controls. Similarly, liver free fatty acids of the diabetics had higher levels of LA (P=0.0001), DHGLA (P=0.001), AA (P=0.001), n-6 metabolites (P=0.002), total n-6 (P=0.0001), ALA (P=0.003), EPA (P=0.015), docosapentaenoic (22:5n-3, P=0.003), DHA (P=0.002), n-3 metabolites (P=0.005) and total n-3 (P=0.001). We conclude that impaired activity of desaturases and/or long chain acyl-CoA synthetase could not explain the higher levels of AA, DHA and n-6 and n-3 metabolites in the diabetics. This seems to be consistent with an alteration in the regulatory mechanism, which directs incorporation of polyunsaturated fatty acids either into triacylglycerols or phospholipids.

Topics: Acyl-CoA Dehydrogenase, Long-Chain; alpha-Linolenic Acid; Animals; Arachidonic Acid; Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Experimental; Docosahexaenoic Acids; Fatty Acids, Nonesterified; Female; Linoleic Acid; Liver; Pregnancy; Pregnancy in Diabetics; Rats; Rats, Sprague-Dawley; Triglycerides

Primiparous Angus x Gelbvieh (n = 36) rotationally crossed beef cows (initial BW = 487.9 +/- 10.5 kg, body condition score = 5.5 +/- 0.02) were utilized to determine effects of supplemental safflower seeds high in linoleic (76% 18:2) or oleic (72% 18:1) acid on cow BW change, body condition score, milk production and composition, calf weight gain, cow serum metabolites, and metabolic hormones. On d 3 postpartum, cows were randomly assigned to one of three isonitrogenous dietary supplements with equal total quantity of TDN: corn-soybean control supplement (n = 12); high-linoleate safflower seeds (n = 12); or high-oleate safflower seeds (n = 12). Safflower-seed supplements were formulated to provide 5% DMI as fat. Supplements were individually fed from d 3 postpartum through 90 d postpartum. Cows had ad libitum access to native grass hay (7.8% CP), trace-mineralized salt, and water. Date of parturition was evenly distributed across treatments with all cows calving within 14 +/- 0.8 d. There were no differences (P = 0.65) in total OM intake among treatments. Although cow BW change did not differ (P = 0.33) by treatment, supplementation influenced cow body condition score (P = 0.02) with linoleate-supple-mented cows in higher (P = 0.005) condition overall than oleate-supplemented cows (5.1 +/- 0.06 vs 4.9 +/- 0.06). Twenty-four-hour milk production did not differ (P = 0.68) among treatments. Percentage milk fat was not different at d 30; however, at d 60 and d 90 percentage milk fat was greater (P ( 0.05) in control and oleate-supplemented cows than in linoleate-supplemented cows. Calf BW gains (P = 0.27) and adjusted 205-d weights (P = 0.48) were not affected by supplement treatment. Supplementation did not influence serum concentrations of glucose (P = 0.38), NEFA (P = 0.61), GH (P = 0.29), IGF-I (P = 0.81), insulin (P = 0.26), or IGF-I binding proteins (P > or = 0.11). Days to conception did not differ (P = 0.40) among treatments. Although overall productivity of the primiparous cows and their calves was not altered by safflower-seed supplementation, differential effects were noted between supplements. Oleate supplementation increased percentage milk fat at d 60, and cow body condition score was lower than in linoleate-supplemented cows. Linoleate-supplemented cows had greater body condition scores by 90 d postpartum than either corn-soybean- or oleatesupplemented cows.

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Composition; Body Weight; Cattle; Dietary Supplements; Fats; Female; Lactation; Linoleic Acid; Milk; Oleic Acid; Parity; Postpartum Period; Random Allocation; Reproduction; Safflower Oil; Seeds; Time Factors; Weight Gain

CLA has a range of biological properties, including effects on lipid metabolism and body composition in experimental animals. The prevalent isomer of CLA found in the human diet is 9c,11 t-CLA, and it is predominantly found in products containing fat from ruminant animals. This study investigated the effect of dietary CLA on energy balance in mice. Synthetic CLA reduced body fat in growing male BALB/c mice in a dose-dependent manner over the range 0.25-1.0% w/w CLA in the diet. Weight gain was also reduced at the highest levels of dietary CLA, being only 5.88 +/- 2.68 g/4 mice (mean +/- 1 SD) after 4 wk of 2.0% CLA in the diet, compared with weight gains of 7.51 +/- 2.22 to 8.17 +/- 2.34 g/4 mice in the 0-0.5% CLA groups. There was no significant effect on weight gain if diets contained 0.5% synthetic CLA or less. These results suggest that high levels of a synthetic mixture of CLA isomers modify energy metabolism and body composition and that high levels of synthetic CLA impair weight gain and reduce body fat pad mass in growing mice.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Diet; Dietary Fats; Dose-Response Relationship, Drug; Energy Metabolism; Linoleic Acid; Male; Mice; Mice, Inbred BALB C; Motor Activity; Weight Gain

Conjugated linoleic acids (CLA) are a class of positional, geometric, conjugated dienoic isomers of linoleic acid (LA). Dietary CLA supplementation results in a dramatic decrease in body fat mass in mice, but also causes considerable liver steatosis. However, little is known of the molecular mechanisms leading to hepatomegaly. Although c9,t11- and t10,c12-CLA isomers are found in similar proportions in commercial preparations, the respective roles of these two molecules in liver enlargement has not been studied. We show here that mice fed a diet enriched in t10,c12-CLA (0.4% w/w) for 4 weeks developed lipoatrophy, hyperinsulinemia, and fatty liver, whereas diets enriched in c9,t11-CLA and LA had no significant effect. In the liver, dietary t10,c12-CLA triggered the ectopic production of peroxisome proliferator-activated receptor gamma (PPARgamma), adipocyte lipid-binding protein and fatty acid transporter mRNAs and induced expression of the sterol responsive element-binding protein-1a and fatty acid synthase genes. In vitro transactivation assays demonstrated that t10,c12- and c9,t11-CLA were equally efficient at activating PPARalpha, beta/delta, and gamma and inhibiting liver-X-receptor. Thus, the specific effect of t10,c12-CLA is unlikely to result from direct interaction with these nuclear receptors. Instead, t10,c12-CLA-induced hyperinsulinemia may trigger liver steatosis, by inducing both fatty acid uptake and lipogenesis.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Dietary Fats; DNA-Binding Proteins; Energy Metabolism; Fatty Liver; Female; Gene Expression Regulation; Hyperinsulinism; Insulin; Isomerism; Linoleic Acid; Liver; Liver X Receptors; Mice; Orphan Nuclear Receptors; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Transcription Factors

We examined the effect of altering the linoleic acid (LA, 18:2n-6) to alpha-linolenic acid (ALA, 18:3n-3) ratio in the dietary fats of 3 day old piglets fed formula for 3 weeks. The LA-ALA ratios of the experimental formulas were 0.5:1, 1:1, 2:1, 4:1, and 10:1. The level of LA was held constant at 13% of total fats while the level of ALA varied from 1.3% (10:1 group) to 26.8% (0.5:1 group). Incorporation of the n-3 long chain PUFA EPA and 22:5n-3 into erythrocytes, plasma, liver, and brain tissues was linearly related to dietary ALA. Conversely, incorporation of DHA into all tissues was related to dietary ALA in a curvilinear manner, with the maximum incorporation of DHA appearing to be between the LA-ALA ratios of 4:1 and 2:1. Feeding LA-ALA ratios of 10:1 and 0.5:1 resulted in lower and similar proportions of DHA in tissues despite the very different levels of dietary ALA (1.3 vs. 26.8% of total fats, respectively). These results are relevant to term infant studies in that they confirm our earlier findings of the positive effect on DHA status by lowering the LA-ALA ratio from 10:1 to 3:1 or 4:1, and they predict that ratios of LA-ALA below 4:1 would have little further beneficial effect on DHA status.

Topics: alpha-Linolenic Acid; Animals; Animals, Newborn; Body Weight; Brain Chemistry; Chromatography, Gas; Dietary Fats; Docosahexaenoic Acids; Erythrocytes; Female; Linoleic Acid; Liver; Nutritional Physiological Phenomena; Swine

The supply of polyunsaturated fatty acids (PUFA) is important for optimal fetal and postnatal development. We have previously shown that leptin levels in suckling rats are reduced by maternal PUFA deficiency. In the present study, we evaluated the effect of maternal dietary intake of (n-3) and (n-6) PUFA on the leptin content in rat milk and serum leptin levels in suckling pups. For the last 10 days of gestation and throughout lactation, the rats were fed an isocaloric diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet), or soybean oil (n-6/n-3 diet). Body weight, body length, inguinal fat pad weight, and adipocyte size of the pups receiving the n-3 diet were significantly lower during the whole suckling period compared with n-6/n-3 fed pups. Body and fat pad weights of the n-6 fed pups were in between the other two groups at week one, but not different from the n-6/n-3 group at week 3. Feeding dams the n-3 diet resulted in decreased serum leptin levels in the suckling pups compared with pups in the n-6/n-3 group. The mean serum leptin levels of the n-6 pups were between the other two groups but not different from either group. There were no differences in the milk leptin content between the groups. These results show that the balance between the n-6 and n-3 PUFA in the maternal diet rather than amount of n-6 or n-3 PUFA per se could be important for adipose tissue growth and for maintaining adequate serum leptin levels in the offspring.

Topics: Adipocytes; Adipose Tissue; alpha-Linolenic Acid; Analysis of Variance; Animals; Animals, Suckling; Body Weight; Diet; Dietary Fats, Unsaturated; Fatty Acids; Female; Leptin; Linoleic Acid; Milk; Pregnancy; Prenatal Nutritional Physiological Phenomena; Rats; RNA, Messenger

1. Effects of linoleic and linolenic acid provided via different oil sources on total antibody (Ab) titres, Ab isotypes after primary and secondary immunisation, and cutaneous hypersensitivity (CH) responses to bovine serum albumin (BSA) and maleyl-BSA, respectively, were studied in pullets fed on one of 4 diets. The diets were the basal control diet enriched with either sunflower oil or safflower oil as sources of linoleic acid, and linseed oil as a source of linolenic acid, tested against a control diet supplemented with animal fat. 2. Total Ab and immunoglobulin (Ig) isotype responses to BSA were affected by diet after primary, and diet x immunisation effects after secondary immunisation. Higher total Ab and IgG titres to BSA were found especially after primary immunisation in birds given the sunflower oil enriched diet, whereas birds given sunflower oil mounted significantly lower IgM titres to BSA after primary and secondary immunisation. The antibody responses to maleyl-BSA were affected by diet after primary, and immunisation x diet interactions after secondary immunisation. Sunflower oil enhanced total and IgG Ab titres to maleyl-BSA after primary immunisation, but decreased IgM titres to maleyl-BSA after primary and secondary immunisation. Cutaneous hypersensitivity responses to BSA and maleyl-BSA were not affected by the diet. 3. It is concluded that modulation of the magnitude and isotype of Ab responses of poultry to T cell-dependent antigens is affected not only by type of essential fatty acids, but also by their source. In the present study the n-6 source, sunflower oil, showed strong enhancement of primary Ab responses, directed to both Th2 and Th1 antigens. On the other hand, the different effects of safflower oil imply that constituents other than n-6 acids within dietary plant oils may affect immune responsiveness. 4. The relationship between magnitude and isotype of Ab responsiveness, type of antigen, and essential fatty acids is discussed.

Topics: alpha-Linolenic Acid; Animal Feed; Animals; Antibody Formation; Body Weight; Chickens; Dietary Fats, Unsaturated; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Immunization; Immunization, Secondary; Linoleic Acid; Plant Oils; Random Allocation; Safflower Oil; Serum Albumin, Bovine; Sunflower Oil

To compare the effectiveness of a conjugated linoleic acid (CLA) isomer mixture (mCLA) with each main isomer [trans-10,cis-12 CLA (CLA10,12) and cis-9,trans-11 CLA (CLA9,11)] in causing body lipid loss and adipose tissue apoptosis.. Mice selected over 16 generations for high (MH) or low (ML) energy expenditure and a control group (MC) were fed diets containing either soy oil or soy oil plus mCLA, CLA10,12, or CLA9,11 for 5 days in one study and 14 days in a second study.. Mice fed mCLA or CLA10,12 had less body lipid (p < 0.05), smaller retroperitoneal fat pads (p < 0.05), and ate less (p < 0.01) than mice fed no CLA or CLA9,11 for 5 days. Mice consuming 1% mCLA or 0.5% CLA10,12 gained less weight (p < 0.01) and had less body lipid (p < 0.05) and smaller epididymal (p < 0.05) and retroperitoneal fat pads (p < 0.01) than mice consuming either control or 0.5% CLA9,11-containing diets for 14 days. Only mCLA and CLA10,12 increased apoptosis in retroperitoneal fat pads (p < 0.01). The effects of mCLA and CLA10,12 were independent of genetic line except for the effect on adipocyte apoptosis. Mice of the MH line were slightly less sensitive than MC or ML mice to CLA-induced adipose tissue apoptosis.. CLA10,12, but not CLA9,11, can induce both body fat loss and adipose apoptosis. Although mice of a genotype with less body fat and greater metabolic rate and feed intake appear less sensitive, these CLA effects are robust for mice of varying metabolic background.

Topics: Adipocytes; Adipose Tissue; Animals; Apoptosis; Body Composition; Body Weight; Diet; Eating; Epididymis; Female; Linoleic Acid; Lipids; Male; Mice; Mice, Inbred ICR; Organ Size; Retroperitoneal Space

In this study, the effect of varying doses of conjugated linoleic acid (CLA) on the growth of transplanted hepatoma dRLh-84 cells and the relationship between tumor growth and prostaglandin (PG) E2 production or cyclooxygenase (COX)-2 expression were examined. Donryu rats were fed an experimental diet containing 0, 0.1, 0.5, or 2 wt.% CLA for 3 wk, and then dRLh-84 cells were transplanted into the liver. Results show that dietary CLA (0.5 and 2 wt.%) significantly enhanced the growth of the transplanted hepatoma cells compared to the non-CLA diet group at 20 d after cell transplantation. Tumor weight at 10 d after transplantation was also significantly higher in the 2 wt.% CLA group than in non-CLA fed rats. Ten days after transplantation, the PGE2 level in the tumor tissue was shown to be depressed in a CLA dose-dependent manner. Cyclooxygenase-2 (COX-2) mRNA expression in the tumor also tended to be lower in the CLA group than in the non-CLA diet group 10 d after transplantation. Dietary CLA did not affect the tumor phospholipid arachidonic acid level, which is a substrate for PG synthesis. These results indicate that dietary CLA of at least 0.5 wt.% enhances the growth of transplanted dRLh-84 cells in vivo. It is believed that growth promotion of dRLh-84 cells in vivo by CLA cannot be clarified by the PG synthesis dependent mechanism.

Topics: Animals; Blotting, Southern; Body Weight; Cell Division; Cyclooxygenase 2; Dietary Fats, Unsaturated; Dinoprostone; Dose-Response Relationship, Drug; Isoenzymes; Linoleic Acid; Liver; Liver Neoplasms, Experimental; Male; Organ Size; Phospholipids; Prostaglandin-Endoperoxide Synthases; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Tumor necrosis factor-alpha (TNF) is an immunoregulatory cytokine that plays a major role in tumor-induced anorexia and weight loss. Conjugated linoleic acids (CLA) are naturally occurring isomers of linoleic acid that, when added to the diet, improve food intake and body weight in mice injected with TNF. The purpose of the present study was to examine the effects of a diet supplemented with 0.5% CLA on the nutritional status of rats implanted with the Morris 7777 hepatoma. Body weight, food intake, serum levels of insulin-like growth factor, and splenocyte synthesis of TNF were not different in tumor-bearing animals fed CLA versus the control diet. However, insulin levels were increased in both tumor-bearing and control animals given CLA. The 0.5% CLA did not improve the nutritional status nor alter TNF synthesis in hypophagic tumor-bearing rats. The biological significance of increased insulin levels in animals given CLA remains to be determined.

Topics: Analysis of Variance; Animals; Anorexia; Body Weight; Dietary Supplements; Disease Models, Animal; Drug Evaluation, Preclinical; Energy Intake; Insulin; Insulin-Like Growth Factor I; Linoleic Acid; Liver Neoplasms, Experimental; Male; Mice; Nutritional Status; Rats; Rats, Inbred BUF; Tumor Necrosis Factor-alpha; Wasting Syndrome

To examine dietary fat and meat intake in relation to risk of type 2 diabetes.. We prospectively followed 42,504 male participants of the Health Professionals Follow-Up Study who were aged 40-75 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1986. Diet was assessed by a validated food frequency questionnaire and updated in 1990 and 1994. During 12 years of follow-up, we ascertained 1,321 incident cases of type 2 diabetes.. Intakes of total fat (multivariate RR for extreme quintiles 1.27, CI 1.04-1.55, P for trend=0.02) and saturated fat (1.34, 1.09-1.66, P for trend=0.01) were associated with a higher risk of type 2 diabetes. However, these associations disappeared after additional adjustment for BMI (total fat RR 0.97, CI 0.79-1.18; saturated fat 0.97, 0.79-1.20). Intakes of oleic acid, trans-fat, long-chain n-3 fat, and alpha-linolenic acid were not associated with diabetes risk after multivariate adjustment. Linoleic acid was associated with a lower risk of type 2 diabetes in men <65 years of age (RR 0.74, CI 0.60-0.92, P for trend=0.01) and in men with a BMI <25 kg/m(2) (0.53, 0.33-0.85, P for trend=0.006) but not in older and obese men. Frequent consumption of processed meat was associated with a higher risk for type 2 diabetes (RR 1.46, CI 1.14-1.86 for > or = 5/week vs. <1/month, P for trend <0.0001).. Total and saturated fat intake were associated with a higher risk of type 2 diabetes, but these associations were not independent of BMI. Frequent consumption of processed meats may increase risk of type 2 diabetes.

Topics: Adult; Age Factors; Aged; Body Mass Index; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Proteins; Humans; Hypercholesterolemia; Hypertension; Incidence; Linoleic Acid; Male; Meat; Middle Aged; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires

Two experiments were conducted to investigate the influence of dietary conjugated linoleic acid (CLA) on the growth, body composition, abdominal fat accumulation, and meat quality in broilers. In Experiment 1, 50 broilers that were 3 wk old (total of 200 birds) were assigned to one of the four diets containing 0, 0.25, 0.5, or 1% CLA and were fed for 3 wk. In Experiment 2, 40 broilers that were 3 wk old (total of 120 birds) were assigned to one of the three diets containing 0, 2, or 3% CLA and fed for 5 wk. At the end of the 3-wk feeding trial, the average body weight of broilers for Experiment 1 was about 2.20 kg per bird for all treatments. For Experiment 2, after 5-wk feeding trial, the average body weights of birds were 4.04, 3.99, and 3.93 kg for the control, 2% CLA, and 3% CLA groups, respectively, with a non significant reduction in body weight as the levels of dietary CLA increased. There was no difference in abdominal fat weight, the total body fat, and protein content in broilers among the CLA treatments for Experiment 1. However, when the dietary CLA was increased to 2 or 3%, the total body fat content was reduced. The whole body fat content decreased from 14.2% in the control to 11.9 and 12.2% for 2 and 3% CLA, respectively. Dietary CLA at 2 and 3% levels influenced meat quality. After cooking, the breast meat from 2 or 3% dietary CLA treatment was harder and drier, and the color was a little darker than that of the control. These changes could be caused by the decreased unsaturated fatty acid content in meat after CLA feeding, which increased the melting point of the fat.

Topics: Adipose Tissue; Animal Nutritional Physiological Phenomena; Animals; Body Composition; Body Weight; Chickens; Dietary Fats, Unsaturated; Eating; Fatty Acids; Linoleic Acid; Lipids; Poultry Products

We carried out energy balance studies in four groups of young, growing, 5-wk-old Balb-C mice (n = 12/group) that were either food restricted or nonrestricted and fed high fat diets (38 energy%) with or without 0.93 g/100 g conjugated linoleic acid (CLA) for 39 d. The energy in carcasses, excreta and food was measured in a bomb calorimeter. CLA lowered the percentage of the energy intake that was stored in the body from 1.9 +/- 0.8 to -2.3 +/- 0.7% (mean +/- SD, P < 0.05) in the nonrestricted mice and from 1.4 +/- 1.3 to -2.9 +/- 0.7% (P < 0.05) in the restricted mice. Thus, the CLA-treated mice had a net loss of body energy. The percentage of the energy intake eliminated in the excreta increased from 7.6 +/- 0.9% in controls to 8.7 +/- 1.0% (P < 0.05) in the CLA-treated mice that were nonrestricted and from 7.3 +/- 0.8 to 8.4 +/- 0.6 (P < 0.05) in the restricted mice. The amount of energy ingested minus the amount retained in carcasses and excreta equals the energy expenditure. The percentage of the energy intake that was expended as heat increased from 90.5 +/- 1.2 in controls to 93.6 +/- 1.5% (P < 0.05) in the CLA-treated nonrestricted mice and from 91.3 +/- 1.5 to 94.5 +/- 1.0% (P < 0.05) in the restricted mice. The lower energy storage in the CLA-fed mice was accounted for by an increase in the energy expenditure (74%) and by an increase in energy lost in the excreta (26%). Feeding CLA also increased liver weight, which may warrant further studies on the safety of CLA.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Calorimetry; Eating; Energy Metabolism; Feces; Food Deprivation; Linoleic Acid; Liver; Male; Mice; Mice, Inbred BALB C; Organ Size; Safety

The present study compared the effect of dietary conjugated linolenic acid (CLNA) on body fat and serum and liver lipid levels with that of CLA in rats. FFA rich in linoleic acid, a-linolenic acid, CLA, or CLNA were used as experimental fats. Male Sprague-Dawley rats (4 wk old) were fed purified diets containing 1% of one of these experimental fats. After 4 wk of feeding, adipose tissue weights, serum and liver lipid concentrations, serum tumor necrosis factor (TNF)-alpha and leptin levels, and hepatic beta-oxidation activities were measured. Compared with linoleic acid, CLA and, more potently, CLNA were found to reduce perirenal adipose tissue weight. The same trend was observed in the weight of epididymal adipose tissue. CLNA, but not CLA, was found to significantly increase serum and liver TG concentrations. Serum FFA concentration was also increased in the CLNA group more than in the other groups. The activity of beta-oxidation in liver mitochondria and peroxisomes was significantly higher in the CLNA group than in the other groups. Thus, the amount of liver TG exceeded the ability of hepatic beta-oxidation. Significant positive correlation was found between the adipose tissue weights and serum leptin levels in all animals (vs. perirenal: r = 0.557, P < 0.001; vs. epididymal: r = 0.405, P < 0.05). A less significant correlation was found between adipose tissue weights and serum TNF-alpha level (vs. perirenal: r = 0.069, P > 0.1; vs. epididymal: r = 0.382, P < 0.05). Although the mechanism for the specific effect of CLNA is not clear at present, these findings indicate that in rats CLNA modulated the body fat and TG metabolism differently from CLA.

Topics: Adipose Tissue; Adipose Tissue, Brown; alpha-Linolenic Acid; Animals; Body Weight; Carrier Proteins; Dietary Fats, Unsaturated; Feeding Behavior; Ion Channels; Linoleic Acid; Lipid Metabolism; Lipids; Liver; Male; Membrane Proteins; Mitochondrial Proteins; Organ Size; Oxidation-Reduction; Rats; Uncoupling Protein 1

In order to discover the effect of CLA on the body fat size and serum cytokine levels, four groups of male mice were fed diets containing either 1% linoleic acid (LA) or conjugated linoleic acid (CLA) with or without 0.2% sesamin for 8 weeks. The weight gain and feed efficiency were significantly lower in the CLA groups. CLA significantly reduced relative weights (g/100 g body weight) of epididymal and perirenal adipose tissues, in particular the former. Concentrations of serum TNF-alpha and leptin were significantly reduced by dietary CLA. Sesamin did not show additional effects in all of these parameters. There was a positive correlation between cytokine production and body-fat reducing potential of CLA. These results indicated that mice appeared to be a hyperresponder to dietary CLA insofar as the reduction of body fat size is concerned.

Topics: Adipose Tissue; Animals; Body Weight; Cytokines; Dietary Fats; Energy Intake; Energy Metabolism; Linoleic Acid; Linoleic Acids; Male; Mice; Mice, Inbred ICR; Organ Size

I examined the effects of carp oil, oleic acid, linoleic acid and linolenic acid on tumor growth and metastasis to the liver in mice implanted intrasplenically with highly metastatic Lewis lung carcinoma (LLC) tumors. Carp oil (0.1 or 0.2 mL per mouse) significantly reduced tumor growth and metastasis to the liver. Carp oil at 100 or 1000 mg/L inhibited the DNA synthesis in LLC cells, the capillary-like tube formation of human dermal microvascular endothelial cells (HMVEC) at 1000 mg/L and the adherence of LLC cells to HMVEC at 10 to 1000 mg/L (in vitro). Carp oil (0.2 mL per mouse) inhibited the angiogenesis induced by Matrigel supplemented with vascular endothelial growth factor (VEGF) and heparin (in vivo). Antitumor and antimetastatic actions of carp oil might be partly attributable to the inhibition of DNA synthesis in LLC cells and angiogenesis through the inhibition of the adherence of LLC cells to the microvascular endothelium. Oleic acid (0.1 or 0.2 mL per mouse) significantly inhibited the metastasis to the liver, but it had no effect on the primary solid-tumor growth. Oleic acid inhibited the angiogenesis in both in vitro and in vivo models. Oleic acid at 1000 micromol/L inhibited the DNA synthesis in LLC cells but did not affect the DNA synthesis in HMVEC. These inhibitory actions of oleic acid may be attributable to the inhibition of angiogenesis induced by the tumor. Linoleic acid and linolenic acid had no effect on tumor growth or metastasis to the liver.

Topics: alpha-Linolenic Acid; Animals; Biocompatible Materials; Blood Cell Count; Body Weight; Carcinoma, Lewis Lung; Carps; Collagen; DNA; Drug Combinations; Energy Intake; Fish Oils; Humans; Laminin; Linoleic Acid; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neovascularization, Pathologic; Oleic Acid; Organ Size; Proteoglycans; Tumor Cells, Cultured

Dietary antioxidant vitamins and retinol have been proposed to be protective against breast cancer on the basis of their ability to reduce oxidative DNA damage and their role in cell differentiation. Epidemiologic studies have not been convincing in supporting this hypothesis, but women with high exposure to free radicals and oxidative processes have not been specifically considered. We explored these issues in the Swedish Mammography Screening Cohort, a large population-based prospective cohort study in Sweden that comprised 59,036 women, 40-76 years of age, who were free of cancer at baseline and who had answered a validated 67-item food frequency questionnaire. During 508,267 person-years of follow-up, 1,271 cases of invasive breast cancer were diagnosed. Cox proportional hazards models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). There was no overall association between intake of ascorbic acid, beta-carotene, retinol or vitamin E and breast cancer incidence. High intake of ascorbic acid was inversely related to breast cancer incidence among overweight women (HR=0.61; 95% CI 0.45-0.82, for highest quintile of intake among women with body mass index>25 kg/m(2)) and women with high consumption of linoleic acid (HR=0.72; 95% CI 0.52-1.02, for highest quintile of ascorbic acid intake and average consumption of more than 6 grams of linoleic acid per day). Among women with a body mass index of 25 or below, the hazard ratio for breast cancer incidence was 1.27 (95% CI 0.99-1.63), comparing the highest to the lowest quintile of ascorbic acid intake. Consumption of foods high in ascorbic acid may convey protection from breast cancer among women who are overweight and/or have a high intake of linoleic acid.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Body Weight; Breast Neoplasms; Cell Differentiation; Cohort Studies; Diet; DNA Damage; Female; Follow-Up Studies; Humans; Linoleic Acid; Mammography; Middle Aged; Oxygen; Proportional Hazards Models; Surveys and Questionnaires; Sweden; Vitamin A; Vitamin E

Dietary lipid quantity and quality have recently been shown to affect serum leptin levels in adult rats. Moreover, suckling pups from dams fed a high fat diet had increased serum leptin levels. The aim of the present study was to analyze the influence of essential fatty acid (EFA) deficiency on serum leptin levels in dams and their pups during the suckling period. For the last 10 days of gestation and throughout lactation, pregnant rats were fed a control or an EFA-deficient (EFAD) diet. The levels of leptin and EFA in the serum of the dams and pups were analyzed 1, 2, and 3 weeks after delivery. In parallel, serum levels of glucose and corticosterone were analyzed in the pups. Low serum leptin levels were found in the control lactating dams during the entire lactation period compared with the age-matched nonlactating animals. The leptin concentrations in the lactating dams fed the EFAD diet were lower compared with those fed the control diet. The serum leptin levels of suckling pups from dams on the EFAD diet were markedly decreased compared with controls (P < 0.05). The reduced serum leptin levels could not be explained by nutritional restriction as evaluated by serum levels of glucose and corticosterone. These results indicate the importance of the EFA composition of the maternal diet for serum leptin levels in both dams and pups. EFA deficiency in lactating dams may cause long-term effects on the pups through dysregulation of leptin and leptin-dependent functions. -- Korotkova, M., B. Gabrielsson, L. A. Hanson, and B. Strandvik. Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups. J. Lipid Res. 2001. 42: 359--365.

Topics: Aging; alpha-Linolenic Acid; Animals; Animals, Suckling; Blood Glucose; Body Weight; Corticosterone; Dietary Fats; Fatty Acids, Essential; Female; Lactation; Leptin; Linoleic Acid; Phospholipids; Rats; Rats, Sprague-Dawley

Conjugated linoleic acid (CLA) has been used experimentally as a dietary supplement to increase lean body weight and to modulate inflammation in a variety of animal species. In addition, human use of dietary CLA as a supplement to regulate body fat has received both scientific and public attention. No reports have been published regarding the effects of dietary CLA on antimicrobial resistance. In this study, we provide evidence that feeding CLA for up to 4 wk does not alter host defense against Listeria monocytogenes in mice. These findings suggest that the anti-inflammatory effects of CLA do not impair cellular immunity to this intracellular pathogen.

Topics: Animals; Body Weight; Female; Linoleic Acid; Listeria monocytogenes; Listeriosis; Liver; Mice; Mice, Inbred Strains; Spleen

In animals, the whole-body content and accumulation of linoleate can be measured and compared with its intake to determine linoleate beta-oxidation. This method can also provide quantitative information about the beta-oxidation of linoleate in humans.. The objectives of the study were to 1) use the wholebody fatty acid balance method to quantify whole-body concentrations of linoleate in humans, 2) estimate the distribution of linoleate between adipose and lean tissue, and 3) assess the effect of weight loss on linoleate stores and beta-oxidation in obese humans.. Nine healthy obese men underwent supervised weight loss for 112 d (16 wk). Magnetic resonance imaging data and fatty acid profiles from fat biopsies were both used to determine linoleate stores in adipose and lean tissue and in the whole body. Linoleate beta-oxidation was calculated as intake - (accumulation + excretion).. Mean weight loss was 13 kg and linoleate intake was 24 +/- 6 mmol/d over the study period. Whole-body loss of linoleate was 37 +/- 18 mmol/d, or 28% of the level before weight loss. Combining the intake and whole-body loss of linoleate resulted in linoleate beta-oxidation exceeding intake by 2.5-fold during the weight-loss period.. All dietary linoleate is beta-oxidized and at least an equivalent amount of linoleate is lost from the body during moderate weight loss in obese men. The method studied permits the assessment of long-term changes in linoleate homeostasis in obese humans and may be useful in determining the risk of linoleate deficiency in other conditions.

Topics: Adipose Tissue; Adult; Body Weight; Cholesterol Esters; Energy Intake; Exercise; Fatty Acids, Unsaturated; Homeostasis; Humans; Linoleic Acid; Magnetic Resonance Imaging; Male; Middle Aged; Obesity; Oxidation-Reduction; Tissue Distribution; Weight Loss

The objective of the study was to determine if consumption of conjugated linoleic acid (CLA) by mice could induce apoptosis in adipose tissue. Other objectives were to determine the influence of feeding mice CLA for < or =2 weeks on body fat, energy expenditure, and feed intake.. A mixture of CLA isomers (predominantly c9,t11 and t10,c12) was included in the AIN-93G diet at 0, 1, and 2%, and fed to mice for 12 days (Trial 1), or was included at 2% and fed to mice for 0, 5, and 14 days (Trial 2). Feed intake was measured daily and energy expenditure was determined by direct calorimetry on day 9 in Trial 1. Retroperitoneal fat pads were analyzed for apoptosis by determination of DNA fragmentation.. Dietary CLA reduced feed intake by 10% to 12% (p < 0.01), but either did not influence or did not increase energy expenditure as indicated by heat loss. Body weight was not influenced by consumption of CLA in Trial 1 but was increased (p < 0.01) by CLA in Trial 2. Weights of retroperitoneal, epididymal, and brown adipose tissues were lower (p < 0.01) in animals fed CLA, although liver weight was increased (p < 0.10; Trial 1) or not changed (Trial 2). Analysis of retroperitoneal fat pad DNA from both trials indicated that apoptosis was increased (p < 0.01) by CLA consumption.. These results are interpreted to indicate that CLA consumption causes apoptosis in white adipose tissue. This effect occurs within 5 days of consuming a diet that contains CLA.

Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Apoptosis; Body Temperature Regulation; Body Weight; Calorimetry; Dietary Fats, Unsaturated; DNA Fragmentation; Eating; Linoleic Acid; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Random Allocation

Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitosamine (intragastrically, i.g.), 7,12-dimethylbenz[a]anthracene (i.g.), 1,2-dimethylhydrazine (subcutaneously) and N-butyl-N-(4-hydroxybutyl)nitrosamine (in drinking water) during the first 3 weeks for initiation, and then administered diet containing 1 or 0.1% CFA-S for 33 weeks. Further groups of animals were treated with carcinogens or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of pre-neoplastic and neoplastic lesions. The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis.

Topics: 1,2-Dimethylhydrazine; 9,10-Dimethyl-1,2-benzanthracene; Animals; Body Weight; Butylhydroxybutylnitrosamine; Carcinogens; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids; Female; Glutathione Transferase; Hyperplasia; Linoleic Acid; Mammary Neoplasms, Experimental; Neoplasms; Nitrosamines; Organ Size; Phosphorylation; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Safflower Oil; Time Factors; Urinary Bladder Neoplasms

We investigated the efficacy of a 4-wk supplementation of conjugated linoleic acid (CLA) as free fatty acid (FFA) or triacylglycerol (TG) on serum leptin concentration, body-fat accumulation, and mitochondrial beta-oxidation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. A significant reduction of serum leptin concentration (42%) and a decrease in the wet weights of perirenal, epididymal, and omental/visceral-adipose tissue in TG-CLA and FFA-CLA groups were found in comparison with the OLETF control group. Both forms of CLA supplementation produced a 5.2% decrease in body weight compared with the control even though food intake was similar in the OLETF groups. Moreover, both forms of CLA enhanced carnitine-palmitoyltransferase activity in brown adipose tissue, perirenal adipose tissue, red gastrocnemius muscle, and liver in comparison with the OLETF control group. Serum concentrations of non-esterified fatty acid and TG also were reduced in rats fed diets supplemented with TG-CLA and FFA-CLA.

Topics: Adipose Tissue; Animals; Body Weight; Carnitine O-Palmitoyltransferase; Eating; Fatty Acids; Fatty Acids, Nonesterified; Leptin; Linoleic Acid; Liver; Male; Oxidation-Reduction; Rats; Rats, Inbred OLETF; Treatment Outcome; Triglycerides; Weight Gain

Recent studies have demonstrated a reduction in body fat in growing animals fed conjugated linoleic acid (CLA). Two experiments were conducted to extend these observations to obese rats so that the mechanism of the actions of CLA might be more easily elucidated. In experiment 1, male lean and obese Zucker rats were fed diets containing either 0 or 0.5% CLA for 5 wk. There was no effect of diet on growth rate or food intake. Dietary CLA reduced retroperitoneal and inguinal fat pad weights in the lean rats but increased fat pad weights in the obese genotype (diet x genotype interaction; P < 0.05). Determination of fat pad cellularity indicated that these changes in fat pad weight were due to a reduction or increase in average fat cell size for the lean and obese Zucker rats, respectively. In experiment 2, we sought to reproduce these effects on fat pad size, as well as to determine the effect of dietary CLA on the catabolic response to bacterial endotoxin injection in obese Zucker rats. Growing female lean and obese Zucker rats were fed diets containing 0 or 0.5% CLA for 8 wk. On d 28, each rat was injected intraperitoneally with lipopolysaccharide from Escherichia coli serotype 055:B5 (1 mg/kg body weight) and body weight was determined over the next 96 h. There was a diet x genotype interaction (P < 0.05) for the body weight response to lipopolysaccharide 24 h postinjection. Lean rats fed CLA lost less weight than did lean controls, but obese rats fed CLA lost more weight than did obese controls. As in the first experiment, there was a diet x genotype (P < 0.05) for the effect of treatment on retroperitoneal fat pad weights determined at the end of the experiment. Lean rats fed CLA had smaller RP fat pads than did lean controls, but obese rats fed CLA once again had heavier RP fat pads than did obese controls. These results indicate that CLA reduces body fat and catabolic response to endotoxin injection in lean Zucker rats but not in the obese genotype. The observed interaction between diet and genotype warrants additional investigation into the specific mechanism(s) of the biological activities of CLA.

Topics: Adipose Tissue; Animals; Body Weight; Dietary Fats, Unsaturated; Eating; Epididymis; Fatty Acids; Female; Genotype; Inguinal Canal; Isomerism; Linoleic Acid; Male; Obesity; Organ Size; Rats; Rats, Zucker; Retroperitoneal Space

Topics: Adipose Tissue; Animals; Basal Metabolism; Body Weight; Energy Metabolism; Humans; Kinetics; Linoleic Acid; Mice; Models, Theoretical; Obesity

Phospholipid fatty acids are major structural components of neuronal cell membranes, which modulate membrane fluidity and hence function. Evidence from clinical and biochemical sources have indicated changes in the metabolism of fatty acids in several psychiatric disorders. We examined the phospholipid fatty acids in the plasma of a population of autistic subjects compared to mentally retarded controls. Our results showed a marked reduction in the levels of 22: 6n-3 (23%) in the autistic subjects, resulting in significantly lower levels of total (n-3) polyunsaturated fatty acids (PUFA) (20%), without significant reduction in the (n-6) PUFA series, and consequently a significant increase in the (n-6)/(n-3) ratio (25%). These variations are discussed in terms of potential differences in PUFA dietary intake, metabolism, or incorporation into cellular membranes between the two groups of subjects. These results open up interesting perspectives for the investigation of new biological indices in autism. Moreover, this might have new therapeutic implications in terms of child nutrition.

Topics: Adolescent; Adult; alpha-Linolenic Acid; Arachidonic Acid; Autistic Disorder; Body Height; Body Weight; Child; Child, Preschool; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Humans; Intellectual Disability; Linoleic Acid; Male; Phospholipids

Uncoupling protein-3 (UCP3) is a mitochondrial carrier protein of as yet undefined physiological function. To elucidate characteristics of its function, we studied the effects of fasting on resting metabolic rate, respiratory quotient, muscle Ucp3 expression, and mitochondrial proton leak in wild-type and Ucp3(-/-) mice. Also analyzed were the fatty acid compositions of skeletal muscle mitochondria in fed and fasted Ucp3(-/-) and wild-type mice. In wild-type mice, fasting caused significant increases in Ucp3 (4-fold) and Ucp2 (2-fold) mRNA but did not significantly affect mitochondrial proton leak. State 4 oxygen consumption was not affected by fasting in either of the two groups. However, protonmotive force was consistently higher in mitochondria of Ucp3(-/-) animals (P = 0.03), and fasting further augmented protonmotive force in Ucp3(-/-) mice; there was no effect in wild-type mitochondria. Resting metabolic rates decreased with fasting in both groups. Ucp3(-/-) mice had higher respiratory quotients than wild-type mice in fed resting states, indicating impaired fatty acid oxidation. Altogether, results show that the fasting-induced increases in Ucp2 and Ucp3 do not correlate with increased mitochondrial proton leak but support a role for UCP3 in fatty acid metabolism.

Topics: Animals; Arachidonic Acid; Basal Metabolism; Body Weight; Calorimetry, Indirect; Carrier Proteins; Docosahexaenoic Acids; Energy Metabolism; Fasting; Fatty Acids; Food; Ion Channels; Kinetics; Linoleic Acid; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mitochondria, Muscle; Mitochondrial Proteins; Muscle, Skeletal; Organ Size; Oxygen Consumption; Palmitic Acid; Proteins; Protons; RNA, Messenger; Stearic Acids; Uncoupling Protein 2; Uncoupling Protein 3

Cytochrome P4502E1 (CYP2E1) induction by ethanol contributes to alcoholic liver disease and we found that a mixture of polyunsaturated phosphatidylcholines (PPC), which protects against alcohol-induced liver injury, also decreases CYP2E1. Since dilinoleoylphosphatidylcholine (DLPC) is the major component of PPC, we assessed here whether it is responsible for the protection of PPC by feeding rats for 8 weeks our liquid diet containing ethanol (36% of energy) or isocaloric carbohydrates, with either DLPC (1.5 g/1000 cal), PPC (3 g/1000 cal), or linoleate. CYP2E1 was assessed by Western blots and by two of its enzyme activities: the microsomal ethanol-oxidizing system (MEOS) and p-nitrophenolhydroxylase (PNP). With ethanol, CYP2E1 increased 10-fold, with corresponding rises in PNP and MEOS activities. Compared to linoleate, DLPC significantly decreased cytochrome b(5), total cytochromes P450, CYP2E1 content and its corresponding activities. DLPC decreases ethanol-induced CYP2E1 and should be considered for the prevention of alcoholic liver disease.

Topics: Animals; Blotting, Western; Body Weight; Cytochrome P-450 CYP2E1; Cytochromes b5; Diet; Down-Regulation; Enzyme Induction; Ethanol; Linoleic Acid; Liver; Liver Diseases, Alcoholic; Male; Microsomes, Liver; Organ Size; Phosphatidylcholines; Rats; Rats, Sprague-Dawley

An experiment was conducted to determine the efficacy of dietary conjugated linoleic acid (CLA) as a growth promotant in weanling swine. Weanling pigs (n = 192; 7.6 kg and 29 d of age) were randomly assigned to four treatments that were arranged as a 2 x 2 factorial. Concentrations of dietary CLA (0 or 0.6%) and antibiotics (+/-) constituted the main effect variables. Dietary CLA treatments consisted of a 1% addition of an oil containing 60% CLA isomers or 1% soybean oil, and dietary antibiotic treatments were antibiotics or no antibiotics. The experimental diets were fed for 9 wk in four phases (1, wk 1; 2, wk 2 and 3; 3, wk 4 through 6; and 4, wk 7 through 9), after which all pigs were fed identical medicated diets for the duration of the finishing phase. Live weights were recorded at wk 17 postweaning and at marketing to determine any residual effects of dietary treatments on finisher ADG and days to market. Medicated diets fed during phases 1 and 2 contained 55 mg carbadox/kg; during phase 3 contained 299 mg tilmicosin/kg; and during phase 4 contained 110 mg tylosin and 110 mg sulfamethazine/kg. Pigs fed medicated diets had higher overall ADG than pigs fed unmedicated diets for wk 0 through 9 (P < 0.03). Gain:feed (G:F) was greater for pigs fed medicated diets than for pigs fed unmedicated diets during phase 1 (P < 0.03) and for the duration of the nursery phase (P < 0.03). There were no effects of CLA on ADG, ADFI, or G:F. There were no residual effects of nursery CLA or antibiotics on finisher ADG and days to market. Blood samples collected from a subset of pigs (n = 72) at the completion of phases 2, 3, and 4 were assayed for serum IGF-I and antibody concentrations to porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae. There was a tendency for pigs fed medicated diets to have greater IGF-I concentrations than pigs fed unmedicated diets at the completion of phase 4 (P < 0.06). Pigs fed CLA had greater antibody titers (P < 0.02) to Mycoplasma hyopneumoniae at d 63 than pigs fed diets without CLA. These results indicate that feeding 0.6% dietary CLA did not enhance growth performance in weanling swine and that the use of dietary antibiotics can increase production efficiency in nursery pigs. Furthermore, there were no interactions between CLA and dietary antibiotics on the variables addressed in this study.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Antibodies, Viral; Body Composition; Body Weight; Dietary Fats; Drug Residues; Evaluation Studies as Topic; Female; Insulin-Like Growth Factor I; Linoleic Acid; Male; Mycoplasma; Porcine respiratory and reproductive syndrome virus; Random Allocation; Swine; Treatment Outcome; Weaning

A 19-carbon conjugated diene, conjugated nonadecadienoic acid (CNA), inhibited heparin-releasable lipoprotein lipase and reduced lipid stores in 3T3-L1 adipocytes similarly to conjugated linoleic acid (CLA). When fed to growing mice (0.3% of diet) CNA reduced body fat by 81% whereas CLA reduced body fat by 25%. CLA and CNA differ in length by one carbon atom so they are unlikely to share a common metabolite to account for these observations.

Topics: 3T3 Cells; Adipocytes; Animals; Body Composition; Body Weight; Diet; Fatty Acids, Unsaturated; Glycerol; Isomerism; Linoleic Acid; Lipoprotein Lipase; Mice; Molecular Weight; Triglycerides

The mechanisms underlying the beneficial effects of conjugated linoleic acid (CLA) are unknown, but one hypothesis is that they are mediated by the nuclear receptor, peroxisome proliferator-activated receptor (PPARalpha). In this work, the effect of dietary CLA on body weight gain, body composition, serum lipids and tissue specific PPAR target gene expression was examined in PPARalpha-null mice. Male wild-type or PPARalpha-null mice were fed either a control diet or one containing 0.5% CLA for a period of 4 weeks. Weight gain in wild-type and PPARalpha-null mice fed CLA was similar, and significantly less than controls. Whole body fat content was lower in wild-type and PPARalpha-null mice while whole body protein content was increased in both genotypes fed CLA compared to controls. Serum triglycerides were lowered in both genotypes as a result of dietary CLA. While CLA feeding resulted in specific activation of PPARalpha in liver, alterations in liver, adipose and muscle mRNAs were also found that were independent of PPARalpha genotype including those encoding uncoupling proteins (UCPs), mitochondrial fatty acid oxidizing enzymes, and fatty acid transporter. These results demonstrate that despite specific activation of PPARalpha-dependent gene expression, the influence of CLA on body composition appears to be independent of PPARalpha. Further, CLA causes increased levels of mRNAs encoding lipid metabolizing and mitochondrial uncoupling proteins that likely contribute to the mechanisms underlying reduced fat/increased lean body mass resulting from consumption of dietary CLA.

Topics: Animals; Blood Glucose; Blotting, Northern; Body Composition; Body Weight; Cholesterol; Diet; Gene Expression Regulation; Linoleic Acid; Liver; Mice; Mice, Knockout; Muscle, Skeletal; Organ Size; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Transcription Factors; Triglycerides

The t10c12 isomer of conjugated linoleic acid (CLA) reduces lipid accumulation in adipocytes in part by inhibiting heparin-releasable lipoprotein lipase (LPL) activity. We now show that inhibitors of lipoxygenase (LOX) activity (2-[12-hydroxydodeca-5,10-diynyl]-3,5,6-trimethyl-p-benzoquinone; 5,8,11,14-eicosatetraynoic acid; salicylhydroxamic acid; indomethacin; nordihydroguaiaretic acid (NDGA)) produce a similar inhibitory effect on LPL activity in cultured 3T3-L1 mouse adipocytes. Additionally the LOX inhibitors had no effect on, or inhibited, lipolysis in this cell system (measured as glycerol release). Growing mice fed diet containing 0.1% NDGA for 4 weeks displayed 21% reduction in body fat, which was similar to 23% reduction in body fat produced by feeding diet containing a suboptimal amount of CLA (0.1%) for 4 weeks. Feeding diet containing both 0.1% NDGA and 0.1% CLA resulted in 51% reduction in body fat which was accompanied by significant increases in whole body water and protein. Aspirin, an inhibitor of cyclooxygenase 1 and 2, had no effect on LPL activity in 3T3-L1 adipocytes, did not affect body composition when fed to growing mice, and failed to influence the effects of CLA on LPL activity in 3T3-L1 cells or body composition in mice. These findings appear to provide new perspectives and insights into the relationships between CLA, eicosanoids, the control of lipid accumulation in adipocytes, and effects of CLA on the immune system.

Topics: 3T3 Cells; Adipocytes; Adipose Tissue; Animals; Body Composition; Body Weight; Heparin; Linoleic Acid; Lipoprotein Lipase; Lipoxygenase Inhibitors; Masoprocol; Mice

We investigated the dose-effect of the long-term intake of conjugated linoleic acid (CLA) on the energy metabolism and fat accumulation in mice. Five-week-old male Std ddY mice were fed on a diet containing none (control), 0.25%, 0.5% or 1.0% CLA for 4 or 8 weeks. The body weight was lower in the CLA groups than in the control group, and significant differences were detected between the 1.0% CLA group and the control group at both 4 and 8 weeks. The epididymal and perirenal adipose tissue weights were significantly lower in the CLA groups than in the control group. The liver weight and hepatic triglyceride values were higher in the 1.0% CLA group than in the other groups. The metabolic rate was measured after 8 weeks by using a gas analyzer. The oxygen consumption of the mice in the CLA groups was significantly higher than that of the control mice. Since there was a significant effect on the mice supplemented with 0.25% CLA, low concentration of CLA is suggested to suppress the body fat accumulation and increase the energy metabolism.

Topics: Adipose Tissue; Animals; Basal Metabolism; Body Weight; Calorimetry, Indirect; Energy Metabolism; Glycogen; Linoleic Acid; Liver; Male; Mice; Organ Size; Oxygen Consumption; Random Allocation; Statistics, Nonparametric; Triglycerides

Three experiments investigated effects of jejunal lipid infusions given on 4 or 21 consecutive days in adult, male Sprague-Dawley rats. In experiment 1, 7-h infusions of linoleic or oleic acid (0.2 ml/h for 7 h; total load = 11.5 kcal) on 4 consecutive days reduced total intake (ad libitum consumption of the liquid diet Boost, Mead Johnson, plus load) by approximately 15% and decreased weight gain compared with 4-day tests with saline administration. In experiment 2, linoleic acid at 0.1 ml/h for 7 h (5.7 kcal) was ineffective, whereas the same load delivered in 3.5 h produced effects similar in magnitude to those in the first experiment. In experiment 3, jejunal infusions of linoleic acid (0.2 ml/h for 7 h) on 21 consecutive days reduced mean total intake by 16%, body weight by 10%, and carcass fat by 48% compared with controls receiving saline. The net decrease in caloric intake may reflect the combined activation of pre- and postabsorptive mechanisms, and it suggests a possible treatment for obesity.

Topics: Adipose Tissue; Animals; Body Weight; Eating; Jejunum; Linoleic Acid; Male; Oleic Acid; Rats; Rats, Sprague-Dawley

The effects of added dietary fat type and level on broiler breeder performance were evaluated in two trials. In Trial 1, diets included no added fat (NAF) or 3.0% added poultry fat (PF) for individual bird energy intakes of 430 and 467 kcal/d at peak production (PCD), or 1.5% PF or 3.0% corn oil (CO) at 449 PCD. In Trial 2, diets contained NAF, 1.5 or 3.0% added CO or PF, or 3.0% lard (LA) for peak energy intakes of 463 PCD. All diets in Trial 2 were isocaloric and isonitrogenous. Feeding of experimental diets was initiated when breeders were 22 wk old in both trials, and hen BW was measured at various weeks between 22 and 47 wk in Trial 1 and between 27 and 65 wk in Trial 2. Egg production, egg weight (EW), eggshell quality, and hatchability were recorded at various weeks between 24 and 48 wk in Trial 1 and between 27 and 64 wk in Trial 2. Body weights and EW increased progressively, and eggshell quality fluctuated variably with age. Egg production peaked between Weeks 32 and 35, and hatchability was significantly depressed at Week 63. Egg weight and hatchability were not affected by dietary treatment; however, BW increased with energy level in the diet between Weeks 27 and 47. Body weight was also higher in birds fed 1.5 or 3.0% added fat compared with NAF and was higher in birds fed LA compared with CO at the 3.0% level. Egg specific gravity and shell weight per unit of surface area at Week 41 were increased by feeding low or high energy compared with moderate energy, and relative eggshell conductance was increased by using moderate compared with high energy diets and by feeding 1.5% PF compared with 3.0% PF. Egg specific gravity was increased by PF when compared with CO across fat level at Weeks 26 and 47 and by LA when compared with PF across fat level and breeder age. These data suggest that certain dietary energy and fat regimens may affect BW and eggshell quality without associated effects on EW and hatchability at various breeder ages.

Topics: Age Factors; Animal Feed; Animals; Body Weight; Breeding; Chickens; Corn Oil; Dietary Fats; Eggs; Energy Intake; Fatty Acids, Unsaturated; Female; Incubators; Linoleic Acid; Male; Oviposition; Random Allocation; Seasons

We investigated the basis for the reduction in fat pad size in rats fed conjugated linoleic acid (CLA). In the first study, growing female Sprague-Dawley rats (initial weight150 g) were fed diets containing 0, 0.25 and 0.5 g/100 g diet of a purified (97% CLA) and 0.5% of a feed-grade (55% CLA) source of CLA for 5 wk to determine the effects on growth performance and fat mass. There was no effect of CLA on growth rate or food intake. Dietary CLA reduced retroperitoneal fat pad weight 13, 25 and 32% in rats fed 0.25 and 0. 5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.05). Similar effects were observed in the parametrial fat pad. The reduced pad size was due to smaller adipocyte size rather than a reduced cell number. Relative to the control group, mean cell volume was 15, 28 and 29% lower in tissue from rats fed 0.25 and 0.5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.01). In the second study, rats were fed CLA (0 vs. 0.5%) for 7 or 49 d. Reductions in fat pad weight were observed within 7 d. In addition, the effects of CLA on energy metabolism were studied in the chronically fed rats. There were no significant effects of CLA on oxygen consumption, CO(2) or heat production. During wk 4 of feeding, but not at other times, there was a 5% lower respiratory quotient in CLA-fed rats (P < 0.05). There was a time-dependent accumulation of CLA in adipose tissue and a decrease in monounsaturated fatty acids. These results suggest that the reduction in fat mass in rats fed CLA can be accounted for by a reduction in cell size rather than a change in cell number.

Topics: Adipose Tissue; Animals; Body Weight; Cell Count; Cell Size; Diet; Energy Metabolism; Female; Linoleic Acid; Organ Size; Rats; Rats, Sprague-Dawley

The present study was designed to investigate the effects of conjugated linoleic acid (CLA) on yolk usage and circulating very low density lipoproteins (VLDL) during incubation (Day 15) and through 6 d post-hatch. Eggs enriched with CLA were obtained from hens subjected to the following treatments. Group A hens served as the control group, Group B hens received 1 g CLA every other day, Group C hens received 1 g CLA every 4th d, and Group D hens were sham-supplemented with 1 g safflower oil every other day. Enrichment with CLA did not effect fertility, hatch of fertile, BW, or yolk-free BW of embryos or chicks. However, there were significant changes in relative yolk sac weight (RYW) and composition of circulating VLDL particles. Across all dietary treatments (Groups B, C, and D), 15-d embryos had smaller RYW compared with Group A embryos; this difference remained through 2 d posthatch. During that period (15 d of incubation through 2 d posthatch), however, embryos and chicks from Group B hens exhibited a unique absorption pattern such that little to no yolk was utilized between hatch and 2 d posthatch, a period normally characterized by high yolk lipid utilization. Similar to the RYW effects, VLDL particles were also altered by hen-induced treatment. Specifically, at hatch, chicks from Group A hens had the highest percentage of triglycerides (TG) within their VLDL particles compared with chicks from hens under all other treatments. This trend in VLDL particles was continued at 4 d posthatch. The present study demonstrates that CLA enrichment of eggs alters relative yolk sac absorption and the composition of circulating VLDL particles.

Topics: Animals; Animals, Newborn; Body Weight; Chick Embryo; Chickens; Cholesterol Esters; Egg Yolk; Female; Linoleic Acid; Lipids; Lipoproteins, VLDL; Organ Size; Phospholipids; Triglycerides; Yolk Sac

This study was designed to determine the amount of conjugated linoleic acid (CLA) incorporated into egg lipids after dietary CLA supplementation. Single Comb White Leghorn laying hens (n = 40; 28 wk old) were randomly assigned to four treatments of varying CLA levels (0, 0.01, 0.5 and 1 g CLA/kg diet). Eggs were collected daily for 36 d. Feed consumption and body weight were monitored. CLA content of egg yolk lipid was analyzed by gas-liquid chromatography. Birds fed 0.5 and 1.0 g CLA/kg feed had significantly more CLA in the egg yolk lipid vs. control and 0.01 g CLA/kg diet groups after 7 d (P < 0.0004). Incorporation of CLA into egg lipid was highest on d 24 and 36. CLA enrichment in egg lipid in the 1.0 g CLA/kg diet group was similar to that in ruminant animal food products, approximately 3 mg CLA/g fat.

Topics: Animal Feed; Animals; Body Weight; Chickens; Egg Yolk; Eggs; Energy Intake; Fatty Acids; Isomerism; Linoleic Acid; Lipid Metabolism

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of APC:(Min/+) mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.

Topics: 6-Ketoprostaglandin F1 alpha; alpha-Linolenic Acid; Animals; Body Weight; Dietary Fats; Dinoprostone; Docosahexaenoic Acids; Eating; Fatty Acids; Fatty Acids, Omega-3; gamma-Linolenic Acid; Genes, APC; Intestinal Neoplasms; Intestines; Linoleic Acid; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Phospholipids

Topics: Arachidonic Acid; Body Weight; Breath Tests; Diet, Fat-Restricted; Female; Gas Chromatography-Mass Spectrometry; Humans; Isotope Labeling; Lactation; Linoleic Acid; Milk, Human; Time Factors

We investigated in bile duct-ligated (BDL) and sham-operated control rats whether the frequent presence of essential fatty acid deficiency in cholestatic liver disease could be related to linoleic acid malabsorption, altered linoleic acid metabolism, or both. In plasma of BDL rats, the triene-to-tetraene ratio, a biochemical marker for essential fatty acid deficiency, was increased compared with controls (0.024 +/- 0.004 vs. 0.013 +/- 0.001; P < 0.05). Net and percentage of dietary linoleic acid absorbed were decreased in BDL rats compared with control rats (1.50 +/- 0.16 mmol/day and 81.3 +/- 3.3% vs. 2.08 +/- 0.07 mmol/day and 99.2 +/- 0.1%, respectively; each P < 0.001). At 24 h after [(13)C]linoleic acid administration, BDL rats had a similar ratio of plasma [(13)C]arachidonic acid to plasma [(13)C]linoleic acid concentration compared with control rats. Delta(6)-Desaturase activity was not significantly different in hepatic microsomes from control or BDL rats. At 3 h after [(13)C]linoleic acid administration, plasma appearance of [(13)C]linoleic acid and cumulative expiration of (13)CO(2) were decreased in BDL rats, compared with controls (by 54% and 80%, respectively). The present data indicate that the impaired linoleic acid status in cholestatic liver disease is mainly due to decreased net absorption and not to quantitative alterations in postabsorptive metabolism.

Topics: Animals; Bile Ducts; Biomarkers; Body Weight; Cholestasis; Disease Models, Animal; Energy Intake; Intestinal Absorption; Ligation; Linoleic Acid; Liver; Male; Rats; Rats, Wistar

The purpose of this study was to examine whether conjugated linoleic acid (CLA) supplementation in human diets would enhance indices of immune status as reported by others for animal models. Seventeen women, 20-41 yr, participated in a 93-d study conducted in two cohorts of 9 and 8 women at the Metabolic Research Unit of Western Human Nutrition Research Center. Seven subjects were fed the basal diet (19, 30, and 51% energy from protein, fat, and carbohydrate, respectively) throughout the study. The remaining 10 subjects were fed the basal diet for the first 30 d, followed by 3.9 g CLA (Tonalin)/d for the next 63 d. CLA made up 65% of the fatty acids in the Tonalin capsules, with the following isomeric composition: t10, c12, 22.6%; c11, t13, 23.6%; c9, t11, 17.6%; t8, c10, 16.6%; and other isomers 19.6%. Most indices of immune response were tested at weekly intervals, three times at the end of each period (stabilization/intervention); delayed-type hypersensitivity (DTH) to a panel of six recall antigens was tested on study day 30 and 90; all subjects were immunized on study day 65 with an influenza vaccine, and antibody titers were examined in the sera collected on day 65 and 92. None of the indices of immune status tested (number of circulating white blood cells, granulocytes, monocytes, lymphocytes, and their subsets, lymphocytes proliferation in response to phytohemagglutinin, and influenza vaccine, serum influenza antibody titers, and DTH response) were altered during the study in either dietary group. Thus, in contrast to the reports with animal models, CLA feeding to young healthy women did not alter any of the indices of immune status tested. These data suggest that short-term CLA supplementation in healthy volunteers is safe, but it does not have any added benefit to their immune status.

Topics: Adult; Antibodies; Body Weight; Cohort Studies; Diet; Dose-Response Relationship, Drug; Fatty Acids; Female; Humans; Hypersensitivity; Immune System; Influenza Vaccines; Leukocytes; Linoleic Acid; Lymphocytes; Placebos; Random Allocation; Time Factors

The effect of the dietary linoleate (LA)/alpha-linolenate (LNA) balance during development on the brain lipid composition, reproductive outcome and behavior of rats was studied. Female rats were fed on experimental diets during pregnancy and the resulting pups for 16 weeks. The dietary LA/LNA ratios were 1.07 (LA1), 2.64 (LA2), 4.45 (LA3), 7.68 (LA4) and 10.35 (LA5). The relative content of docosahexaenoate (DHA) in the brain of pups tended to increase with decreasing LA/LNA ratio at 0 and 3 weeks, while the level of DHA was maintained constant at 16 weeks regardless of the dietary LA/LNA ratio. The learning ability was measured at 12 weeks of age, and there was no difference among the groups. In an open field test, the exploratory index was significantly lower in the LA1 group than in the LA2 group. The LA1 group had a smaller litter size and lower survival rate than the other groups. We conclude that if the diet contained appropriate amounts and balance of LA and LNA, it was possible for rats to synthesize an appropriate amount of DHA and have normal behavioral activity without DHA supplementation.

Topics: alpha-Linolenic Acid; Animals; Body Weight; Brain; Dietary Fats, Unsaturated; Eating; Female; Linoleic Acid; Lipid Metabolism; Male; Rats; Sexual Behavior, Animal

The activity of delta6-desaturase of linoleic acid, a rate-limiting step in the formation of arachidonic acid, is decreased in animal models of severe, uncontrolled diabetes. The aim of the study was to measure the activity of liver microsomal delta6-desaturase of spontaneously diabetic BioBreeding/Edinburgh rats receiving subcutaneous insulin daily and of genetically related nondiabetic animals. The activity of delta6-desaturase was then compared with indices of activity (plasma lipid fatty acid product/precursor ratios) frequently used in human studies. Diabetic rats treated with insulin had 75 +/- 8% of the activity of microsomal delta6-desaturase of nondiabetic controls (P < 0.05). Insulin withdrawal tended to reduce the activity further (61% of control), although the activity did not differ from insulin-treated diabetic rats. The ratio of plasma phospholipid or cholesteryl ester gamma-linolenic over linoleic acid was not decreased in insulin-treated diabetic rats. By contrast, the ratio of gamma-linolenic over linoleic acid of microsomes was almost three-fold higher in insulin-treated diabetic rats (P < 0.05). The gamma-linolenic over linoleic acid ratio as an index of activity gave inconsistent results in insulin-deprived rats. The ratio of gamma-linolenic over linoleic acid of cholesteryl esters did not differ between control and diabetic rats, nor did it correlate with microsomal delta6-desaturase activity. Furthermore, the index of delta6-desaturase activity, derived from the fatty acid composition of microsomal phospholipids, did not correlate with microsomal delta6-desaturase activity. Diabetes, even when controlled by regular insulin injections, reduces the metabolism of linoleic acid, but the effect is less than previously published. The fatty acid compositions of plasma and liver microsomal lipids are not reliable indices of delta6-desaturase activity in diabetes.

Topics: Animals; Blood Glucose; Body Weight; Cholesterol Esters; Diabetes Mellitus, Experimental; Fatty Acid Desaturases; Fatty Acids; Insulin; Linoleic Acid; Linoleoyl-CoA Desaturase; Liver; Male; Microsomes, Liver; Phospholipids; Rats; Rats, Wistar

The present study was carried out to examine if the positional distribution of medium-chain fatty acid (MCF) in dietary synthetic fat influences lymphatic transport of dietary fat and the chemical composition of chylomicrons in rats with permanent cannulation of thoracic duct. Four types of synthetic triacylglycerol were prepared: (i) sn-1 (3) MCF-sn 2 linoleic acid, (ii) interesterified sn-1(3) MCF-sn 2 linoleic acid, (iii) sn-2 MCF-sn-1(3) linoleic acid, and (iv) interesterified sn-2 MCF-sn-1(3) linoleic acid. A purified diet composed of equal amounts of the synthetic fat and cocoa butter was given to rats with permanent lymph duct cannulation. The positional distribution of MCF in the dietary fat had no significant effect on the lymph flow, triacylglycerol output, phospholipid output, lipid composition of chylomicrons, or the particle size. The positional distribution of MCF in the synthetic triacylglycerol was maintained in the chylomicron triacylglycerol. These results showed that MCF in the dietary triacylglycerol is transported into lymphatics and the positional distribution is well preserved in chylomicron triacylglycerol.

Topics: Animals; Biological Transport; Body Weight; Chylomicrons; Diet; Dietary Fats; Fatty Acids; Linoleic Acid; Lipid Metabolism; Lymph; Lymph Nodes; Male; Rats; Rats, Sprague-Dawley; Time Factors; Triglycerides

Recent reports have demonstrated that conjugated linoleic acid (CLA) has effects on body fat accumulation. In our previous work, CLA reduced body fat accumulation in mice fed either a high-fat or low-fat diet. Although CLA feeding reduced energy intake, the results suggested that some of the metabolic effects were not a consequence of the reduced food intake. We therefore undertook a study to determine a dose of CLA that would have effects on body composition without affecting energy intake. Five doses of CLA (0.0, 0.25, 0.50, 0.75, and 1.0% by weight) were studied in AKR/J male mice (n = 12/group; age, 39 days) maintained on a high-fat diet (%fat 45 kcal). Energy intake was not suppressed by any CLA dose. Body fat was significantly lower in the 0.50, 0.75, and 1.0% CLA groups compared with controls. The retroperitoneal depot was most sensitive to the effects of CLA, whereas the epididymal depot was relatively resistant. Higher doses of CLA also significantly increased carcass protein content. A time-course study of the effects of 1% CLA on body composition showed reductions in fat pad weights within 2 wk and continued throughout 12 wk of CLA feeding. In conclusion, CLA feeding produces a rapid, marked decrease in fat accumulation, and an increase in protein accumulation, at relatively low doses without any major effects on food intake.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Dose-Response Relationship, Drug; Eating; Insulin; Leptin; Linoleic Acid; Liver; Male; Mice; Mice, Inbred AKR; Proteins; Spleen; Time Factors; Vacuoles

Decreased bile secretion into the intestine has been associated with low plasma concentrations of essential fatty acids (EFA) in humans. We studied the mechanism behind this relationship by determining the status and absorption of the major dietary EFA, linoleic acid (LA), in control and 1-week bile-diverted rats. The absorption of LA was quantified by a balance method and by measuring plasma concentrations of [13C]LA after its intraduodenal administration. Absolute and relative concentrations of LA in plasma were decreased in bile-diverted rats (P<0.01 and P<0.001, respectively). Fecal excretion of LA was increased at least 20-fold in bile-diverted rats (0.72+/-0.11 vs. 0.03+/-0.00 mmol/day; P<0.0001). Due to increased chow ingestion by bile-diverted rats, net intestinal absorption of LA was similar between bile-diverted and control rats (1.96+/-0.14 vs. 1.91+/-0.07 mmol/day, respectively; P>0.05). After intraduodenal administration of [13C]LA, plasma concentrations were approximately 3-4-fold lower in bile-diverted rats for at least 6 h (P<0.001). Plasma concentrations of both [12C]arachidonic acid and [13C]arachidonic acid were increased in bile-diverted rats (P<0.05). We conclude that decreased plasma concentrations of LA in 1-week bile-diverted rats are not due to decreased net intestinal absorption of LA, but may be related to increased metabolism of LA.

Topics: Animals; Arachidonic Acid; Bile; Body Weight; Dietary Fats, Unsaturated; Diterpenes; Food; Intestinal Absorption; Linoleic Acid; Male; Rats; Rats, Wistar; Retinyl Esters; Vitamin A

Biliary phospholipids have been hypothesized to be important for essential fatty acid homeostasis. We tested this hypothesis by investigating the intestinal absorption and the status of linoleic acid in mdr2 Pgp-deficient mice which secrete phospholipid-free bile. In mice homozygous (-/-) for disruption of the mdr2 gene and wild-type (+/+) mice, dietary linoleic acid absorption was determined by 72 h balance techniques. After enteral administration, [(13)C]-linoleic acid absorption was determined by measuring [(13)C]-linoleic acid concentrations in feces and in plasma. The status of linoleic acid was determined in plasma and in liver by calculating the molar percentage of linoleic acid and the triene:tetraene ratio. Although plasma concentration of [(13)C]-linoleic acid at 2 h after enteral administration was significantly lower in (-/-) compared to (+/+) mice (P

Topics: Animals; Arachidonic Acid; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bile; Body Weight; Carbon Radioisotopes; Eating; Feces; Intestinal Absorption; Linoleic Acid; Male; Mice; Mice, Knockout; Phospholipids

Effects of lipid infusion into postpartum (PP) beef heifers on plasma concentrations of linoleic acid and prostaglandin (PG) F(2alpha) metabolite (PGFM), days to first estrus, and subsequent pregnancy rate were examined. Treatments (n = 5 per group) of 1 L intralipid (20% soybean oil; IL), 1 L 50% dextrose (DEXT; isocaloric to IL), 0.5 L intralipid (0.5 IL), and 1 L physiological saline (SAL) were infused i.v. over 4 h on each of Days 7 through 11 PP. Capacity of the uterus to produce PG was evaluated after i.v. injection of 150 IU of oxytocin (OT) to IL- and DEXT-treated heifers Day 12 PP. Change in plasma concentrations of PGFM from 0 to 4 h was greater for IL-treated heifers than for heifers given other treatments on Day 7 (P = 0.04) and on Day 11 (P = 0.01), but not on Day 9 (P>0.10). Plasma linoleic acid on Day 11 and OT-induced release of PGFM on Day 12 were greater in IL-treated heifers compared with DEXT-treated heifers (P<0.06 and P = 0.01, respectively). There were no significant differences among treatments for mean days to first estrus or pregnancy rate. Infusion of lipid increased systemic concentrations of linoleic acid and increased the capacity of PP heifers to produce uterine PGF(2alpha) as indicated by plasma PGFM concentration after OT injection.

Topics: Animals; Behavior, Animal; Birth Weight; Body Weight; Cattle; Dinoprost; Eating; Estrus; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Female; Fertility; Linoleic Acid; Ovary; Postpartum Period; Pregnancy; Prostaglandins

Diets rich in linoleic acid (LA), an n-6 fatty acid, stimulate the progression of human breast cancer cell solid tumors in athymic nude mice, whereas docosahexaenoic acid (DHA) and eicosapentaenoic acid, long-chain n-3 fatty acids, exert suppressive effects. In the present study we used a novel source of DHA, in triglyceride form, to determine the effects of feeding low levels of the fatty acid on the growth of MDA-MB-231 cells injected into the thoracic mammary fat pads of female nude mice. Four different isocaloric diets were used, all of which provided 20% (wt/wt) total fat. The control diets contained 8% (20 mice) or 4% (50 mice) LA; the n-3 fatty acid-supplemented groups of 50 mice were fed 4% LA-containing diets plus 2% or 4% DHA. The tumor growth rates were reduced significantly in mice fed the 4% LA compared with the 8% LA diet; the addition of 4% DHA to the 4% LA-containing diet produced a further reduction in tumor growth rate (p < or = 0.003 at and after Week 6). The final tumor weights were also reduced in the DHA-fed mice compared with the 8% LA dietary group (2% DHA, p = 0.02; 4% DHA, p = 0.01) and in the 4% DHA-fed mice compared with the 4% LA control group (p = 0.02); a similar trend for mice fed the lower level of DHA did not achieve statistical significance. Tumor prostaglandin E2 concentrations were reduced by feeding the lower LA level; further dose-dependent decreases occurred in the DHA dietary groups and were accompanied by reduced levels of 12- and 15-hydroxyeicosatetraenoic acids. These changes in eicosanoid biosynthesis may have been responsible for the observed decreases in cell proliferation, indicated by suppressed Ki-67 expression, and increases in apoptotic activity, as reflected in TdT-mediated dUTP nick end labeling immunohistochemical staining.

Topics: Animals; Apoptosis; Body Weight; Cell Division; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Eicosanoids; Female; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Ki-67 Antigen; Linoleic Acid; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Tumor Cells, Cultured

Kuwaiti diet is exceptionally rich in fat, carbohydrates and proteins. In addition, subjects in Kuwait are exposed to extreme heat and sun light. Fatty acid profiles of human milk obtained from 19 full breast feeding Kuwaiti mothers were analyzed. Dietary patterns for individual mothers were determined by 24 h dietary recall and food frequency questionnaire. The fatty acid content of human milk was affected by the diet consumed by the lactating mother. The content of long chain polyunsaturated fatty acids (LCP) in human milk lipids did not correlate with their parent fatty acids like linoleic and alpha-linolenic acids. However the human milk LCP were related to the of content of LCP in the maternal diet. Mothers reporting a high fish consumption showed significant amounts of C22:6, omega 3 and C20:5, omega 3 fatty acids. As a general conclusion, breast milk produced by a well nourished mother is better suited to meet the lipid requirements of infants.

Topics: Adult; alpha-Linolenic Acid; Body Weight; Chromatography, Gas; Diet; Fatty Acids; Fatty Acids, Unsaturated; Female; Humans; Kuwait; Linoleic Acid; Milk, Human; Sunlight; Temperature

An experimental model of chronic pancreatitis was induced by a retrograde injection of a viscous solution consisting of zein-oleic acid-linoleic acid (0.05 ml/100 g body weight) into the rat pancreatic duct. Histologic and biochemical changes were investigated over a period of 6 months after induction of this model. The treated rats gained weight, but pancreatic weight decreased with time. Histologically, the widening of acinar lumen and cellular vacuolization occurred within 24 h at the parenchyma neighboring the small ducts filled with the injected solution. Degenerative parenchyma, interstitial edema, and inflammatory cell infiltration were pronounced 1 week later. Thereafter, duct-like tubular complex formation progressed, and the exocrine tissue exhibited marked atrophy of the gland with irregular fibrosis and fat replacement over a period of 6 months. Pancreatic contents of protein, amylase, DNA, and RNA markedly decreased, as did pancreatic weight, whereas hydroxyproline content increased. Oral administration of camostat did not affect pancreatic weight and contents of enzyme in this model. Urinary para-aminobenzoic acid (PABA) excretion in the BT-PABA test decreased to 54% at 6 weeks and 22% at 6 months. Although three quarters of pancreatic immunoreactive insulin (IRI) content was lost after 6 months, overt diabetes did not occur. The results suggest that an obstructive mechanism in the small ducts plays an important role in the genesis and development of chronic pancreatitis.

Topics: Amylases; Animals; Blood Glucose; Body Weight; Chronic Disease; Disease Models, Animal; Esters; Gabexate; Guanidines; Linoleic Acid; Male; Oleic Acid; Organ Size; Pancreas; Pancreatic Ducts; Pancreatitis; Protease Inhibitors; Rats; Rats, Wistar; Solutions; Survival Rate; Zein

The effects of dietary methionine level on the profiles of fatty acids and phospholipids and on the plasma cholesterol concentration were investigated to confirm whether the methionine content of dietary proteins is one of the major factors that cause differential effects on lipid metabolism. The effect of dietary supplementation with eritadenine, which is shown to be a potent inhibitor of phosphatidylethanolamine (PE) N-methylation, was also investigated. Rats were fed six diets containing casein (100 g/kg) and amino acid mixture (86.4 g/kg) differing in methionine content (2.5, 4.5, and 7.5 g/kg) and without or with eritadenine supplementation (30 mg/kg) for 14 d. The ratio of arachidonic to linoleic acid of liver microsomal and plasma phosphatidylcholine (PC) was significantly increased as the methionine level of diet was elevated, indicating that dietary methionine stimulates the metabolism of linoleic acid. The PC/PE ratio of liver microsomes and the plasma cholesterol concentration were also increased by dietary methionine. These effects of methionine were completely abolished by eritadenine supplementation The S-adenosylmethionine concentration in the liver reflected the methionine level of diet. These results support the idea that the differential effects of dietary proteins on lipid metabolism might be ascribed, at least in part, to their different methionine contents, and that methionine might exert its effects through alteration of PE N-methylation.

Topics: Adenine; Animals; Body Weight; Cholesterol; Dietary Proteins; Fatty Acids; Linoleic Acid; Lipids; Liver; Male; Methionine; Methylation; Organ Size; Phosphatidylethanolamines; Phospholipids; Rats; Rats, Wistar; S-Adenosylmethionine

The previous studies showed that dietary 18:2 c,t isomers could be chain-elongated and desaturated to produce unusual 20:4 isomers. The present study was undertaken to determine the minimal amount of 18:2n-6 required to suppress the chain elongation and desaturation of 18:2 c,t isomers in the lactating and neonatal rats when animals were fed 15% partially hydrogenated canola oil diet containing 1.72% energy as 18:2 c,t isomers and varying amounts of free 18:2n-6. These diets induced marginal essential fatty acid (EFA) deficiency states (0.56% energy 18:2n-6) to EFA adequacy (2.56% energy 18:2n-6). After feeding for 50 d, the female animals were mated with males by overnight pairing. After conception, the lactating rats were killed, together with one pup from each dam, at term and day 26 of lactation. Two unusual 20:4 isomers in both maternal and neonatal liver phospholipids were identified as 20:4delta5c,8c,11c,14t and 20:4delta5c,8c,11c,15t, which were derived from 18:2delta9c,12t and 18:2delta9c,13t, respectively. The results showed that 18:2n-6 at about 2.0% of total energy in maternal diet was required to block the production of 20:4delta5c,8c,11c,14t and 20:4delta5c,8c,11c,15t in the maternal liver, whereas 18:2n-6 at about 2.5% of total energy in maternal diet was required to suppress production of these unusual 20:4 isomers in the neonatal liver.

Topics: Animals; Animals, Newborn; Animals, Suckling; Body Weight; Brain; Brain Chemistry; Dietary Fats, Unsaturated; Eating; Fatty Acids; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Isomerism; Lactation; Linoleic Acid; Liver; Male; Organ Size; Phospholipids; Rats; Rats, Wistar; Time Factors

To assess the toxicity of conjugated linoleic acid (CLA) after an extended feeding period, 40 male Fischer 344 rats were given either a basal diet (control) or the same diet supplemented with 1.5% CLA. During the 36-wk study, food disappearance, body weights, and cageside examinations were determined weekly and were found to be unaffected by CLA treatment. On termination, 15 major organs from 10 animals in each treatment group were excised, weighed, and prepared for histopathological evaluation. Results indicated no treatment-related effects. Likewise, haematological analysis of collected cardiac blood did not reveal any significant difference. The average daily intake of CLA by rats in this study was 80-fold and 50-fold greater than the estimated 50th and 90th percentile daily intakes, respectively, for teenage boys. Hence, results from this study indicate a lack of toxicity and support the potential determination for the GRAS status of CLA.

Topics: Adrenal Glands; Animals; Blood Cell Count; Body Weight; Chromatography, Gas; Dietary Fats, Unsaturated; Eating; Food, Formulated; Linoleic Acid; Male; Organ Size; Rats; Rats, Inbred F344; Thymus Gland

Dietary fats are known to influence the fatty acid profile of plasma lipids, including phospholipids which are substrates of lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), an important enzyme in lipoprotein metabolism. We tested whether the dietary fatty acid profile has an effect on LCAT activity in an animal model. Rats were conditioned to eat two meals per day, which were enriched in either palmitic, oleic or linoleic acids, for 10 weeks. Serum was isolated from blood samples taken prior to the meal. The LCAT activity was determined in two ways: (1) by measuring serum cholesterol esterification rates, which are an estimate of LCAT action on endogenous lipoproteins, and (2) by measuring serum LCAT activity levels with excess exogenous substrates, an estimate of LCAT mass. Animals receiving the linoleic acid diet had lower serum concentrations of unesterified cholesterol and triglycerides, if compared with animals fed oleic acid or palmitic acid diets (p < 0.05). Serum LCAT activity levels (measured with excess exogenous substrates) were not different, but both the absolute and fractional rates of cholesterol esterification were highest on the linoleic acid rich diet (p < 0.01), showing that LCAT action on endogenous lipoproteins is improved. No differences were found in serum apolipoprotein B and A-IV concentrations between the dietary groups. Apolipoprotein A-I levels were lowest in the palmitic acid group (oleic and linoleic > palmitic; p < 0.05), and apolipoprotein E levels were highest in the palmitic acid group (palmitic > oleic and linoleic; p < 0.05). It is concluded that a linoleic acid rich diet may cause increased metabolism of serum cholesterol by LCAT in rats. This effect is not due to elevated serum concentrations of LCAT or of its apolipoprotein activators, but most likely to changes in the chemical composition of endogenous lipoprotein substrates. It remains to be established whether the serum cholesterol esterification rates measured in vitro are related to in vivo rates of reverse cholesterol transport.

Topics: Animal Feed; Animals; Body Weight; Cholesterol Esters; Dietary Fats; Linoleic Acid; Lipids; Male; Oleic Acid; Palmitic Acid; Phosphatidylcholine-Sterol O-Acyltransferase; Rats; Rats, Wistar; Triglycerides

Recent epidemiological studies have suggested that weight cycling induced by repeated dieting over time may increase the risk of cardiovascular disease. It is speculated that the increased mortality from coronary heart disease for people with a history of excessive weight cycling could be attributed to change in lipid metabolism. Previous studies have demonstrated that repeated cycling of 100% food restriction followed by ad libitum refeeding caused a depletion of linoleate and alpha-linolenate in rats. The objective of the present study was to test the hypothesis that the weight cycling-induced reduction in linoleate and alpha-linolenate is independent of extent of calorie restriction. Two consecutive weight cycles in three experiments were induced by 100% calorie restriction, 60% calorie restriction, and 36% calorie restriction, respectively, followed by ad libitum refeeding. As the consequence of the two weight cycles, linoleate and linolenate were decreased, whereas myristate, palmitate, and palmitoleate were proportionally increased in carcass and adipose tissue lipids. The results of all three experiments showed a preferential depletion of linoleate and alpha-linolenate without changes in final body weight, total body fat, and adipose tissue pads in the weight-cycled rats. In addition, the triacylglycerol species profile in the adipose tissue of weight-cycled rats was significantly remodeled, with a proportional depletion of linoleate-enriched triacylglycerol species (LLL, LLO, and LLP, where L, O, and P are linoleic, oleic, and palmitic acid, respectively) and a proportional accumulation of palmitate-enriched triacylglycerol species (OPPo, PPPo, and PPP, where Po is palmitoleic acid). We conclude that weight cycling changes the ratio of polyunsaturated fatty acids to saturated fatty acids and remodels the adipose tissue triacylglycerol species profile in rats.

Topics: Adipose Tissue; Animals; Body Weight; Eating; Energy Intake; Fasting; Fatty Acids; Food; Linoleic Acid; Linoleic Acids; Liver; Male; Organ Size; Rats; Rats, Sprague-Dawley; Triglycerides

Conjugated linoleic acid (CLA) is a chemoprotective fatty acid that inhibits mammary, colon, forestomach, and skin carcinogenesis in experimental animals. We hypothesize that the ubiquitous chemoprotective actions of dietary CLA in extrahepatic tissues are dependent upon its role in modulating fatty acid composition and metabolism in liver, the major organ for lipid metabolism. This study begins to evaluate the role of CLA in lipid metabolism by determining the modulation of fatty acid composition by CLA. Female SENCAR mice were fed semipurified diets containing 0.0% (Diet A), 0.5% (Diet B), 1.0% (Diet C), or 1.5% (Diet D) CLA (by weight) for six weeks. Mice fed Diets B, C, and D exhibited lower body weights and elevated amounts of extractable total lipid in livers compared with mice fed diets without CLA (Diet A). Analyses of the fatty acid composition of liver by gas chromatography revealed that dietary CLA was incorporated into neutral and phospholipids at the expense of linoleate in Diets B, C, and D; oleate increased and arachidonate decreased in neutral lipids of CLA diet groups. In addition, increasing dietary CLA was associated with reduced linoleate in hepatic phospholipids. In an in vitro assay, CLA was desaturated to an unidentified 18:3 product to a similar extent as linoleate conversion to gamma-linolenate (9.88, and 13.63%, respectively). These data suggest that CLA may affect metabolic interconversion of fatty acids in liver that may ultimately result in modified fatty acid composition and arachidonate-derived eicosanoid production in extrahepatic tissues. In addition to determining how dietary CLA modulates eicosanoid synthesis, further work is needed to identify enzymatic products that may result from desaturation of CLA.

Topics: Animal Feed; Animals; Body Weight; Fatty Acids; Female; Linoleic Acid; Linoleic Acids; Liver; Mice

The hypocholesterolemic efficacy of various polyunsaturated fatty acids was compared in rats given cholesterol-enriched diets. Capybara oil (CO, linoleic + alpha-linolenic acids), horse oil (HO, alpha-linolenic acid), and sardine oil (SO, eicosapentaenoic + docosahexaenoic acids) were added to diets at 50 g/kg. The weight gain, food intake, and liver weight in the CO-fed group were significantly higher than those in other groups during the 6-wk experimental period. The serum total and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL) cholesterol concentrations of the CO-fed and SO-fed groups were significantly lower than in the HO-fed group after 6 wk. The serum high density lipoprotein cholesterol concentration in the SO-fed group was significantly higher than that in the CO-fed and HO-fed groups. The fecal neutral sterol concentration in the CO-fed group was reduced significantly compared with the other groups, and the fecal bile acid concentration in the HO-fed group was significantly higher than that in the SO-fed group. The results of this study demonstrate that CO lowers the serum total cholesterol and VLDL + IDL + LDL-cholesterol concentrations in the presence of excess cholesterol in the diet as well as SO.

Topics: alpha-Linolenic Acid; Animals; Anticholesteremic Agents; Body Weight; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Energy Intake; Feces; Fish Oils; Fishes; Horses; Linoleic Acid; Linoleic Acids; Lipids; Liver; Male; Oils; Organ Size; Rats; Rats, Inbred F344; Rodentia

In this study, we tested the hypothesis that dietary linoleic acid intake controls the arterial blood plasma linoleic acid concentration and the rates of tumor growth and linoleic acid metabolism in vivo. Seven groups of young male Buffalo rats (11-21 rats/group) were given free access to semipurified diets containing different amounts of corn and/or olive oils. Four other groups (7-11 rats/group) were 30% energy-restricted. Each experiment included periods for rat growth and plasma lipid stabilization (6 wk), measurement of mean daily arterial blood plasma fatty acid concentrations (3 wk), surgical implantation of a subcutaneous tissue-isolated hepatoma 7288CTC, tumor growth and harvest (2-4 wk). Linoleic + arachidonic acid (P = 0.007) and oleic acid (P = 0.002) concentrations in arterial blood plasma were increased as dietary intake of linoleic and oleic acids was increased, respectively. In rats given free access to food, tumor growth was directly dependent on the plasma concentrations of linoleic (P < 0.001) and arachidonic acids (P = 0.04). Tumor growth in energy-restricted rats was dependent only on the linoleic acid concentration (P = 0.008). Energy restriction itself caused a growth inhibition independent of plasma linoleic acid. The linoleic acid and total fatty acid concentrations of tumor triacylglycerols were directly dependent on the plasma linoleic acid concentration in rats given free access to food (P = 0.009). Hepatoma 7288CTC (both in vivo and during perfusion in situ) supported a dose-dependent conversion (P < 0.001) of plasma linoleic acid to the mitogen, 13-hydroxy-9, 11-octadecadienoic acid. We conclude that increased arterial blood plasma linoleic acid concentrations, caused by increased dietary intakes, specifically stimulate growth, lipid storage and linoleic acid metabolism in hepatoma 7288CTC in vivo.

Topics: Animals; Arachidonic Acid; Body Weight; Carbon Radioisotopes; Cell Division; Circadian Rhythm; Dietary Fats; Dose-Response Relationship, Drug; Fatty Acids; Linoleic Acid; Linoleic Acids; Lipids; Liver Neoplasms, Experimental; Male; Rats; Rats, Inbred BUF; Triglycerides

This study examined the possible effects of a novel mixture of fatty acids, SR-3 (a specific ratio of alpha-linolenic acids), on brain biochemistry and on learning deficits induced by injection of an agent that induces experimental allergic encephalomyelitis. Treatment with SR-3 caused a decrease in myelin and changes in the fatty acid profile of brain synaptosomes, and a learning deficit. Eighteen days of treatment with SR-3 reversed the biochemical and learning deficit significantly, but did not restore them to normal levels. We propose that, most probably, the main action of SR-3 is the modulation of the cholesterol level, which in turn causes the modulation of the fatty acid profile and enhances learning by allowing improved neuronal communication.

Topics: alpha-Linolenic Acid; Analysis of Variance; Animals; Avoidance Learning; Body Temperature; Body Weight; Brain; Brain Chemistry; Cholesterol; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Fatty Acids, Essential; Learning; Linoleic Acid; Male; Maze Learning; Motor Activity; Myelin Sheath; Rats; Rats, Inbred Lew; Synaptosomes

The effect of linoleic and linolenic acid on antibody (Ab) responses to SRBC and BSA and on growth performance were studied in pullets of three genetically different laying lines. Pullets were fed one of three diets: a control diet, a linoleic acid-enriched diet, or a linolenic acid enriched-diet. The linoleic and linolenic acid enriched-diets were the control diet enriched with either sunflower oil or linseed oil. Two chicken lines divergently selected for high (H) and low (L) Ab responses to SRBC, and a randombred control (C) line were used. Total Ab responses to SRBC were not affected by diet, but in the H line a tendency for higher IgG titers to SRBC after primary immunization were found when birds were fed the linoleic diet. The humoral response to BSA was significantly affected by a line by immunization by diet interaction. In the H line birds, the linoleic diet significantly enhanced Ab titers to BSA as compared to the normal diet and linolenic acid-enriched diet. The linolenic acid-enriched diet significantly decreased Ab titers to BSA in the C line birds. No dietary effects on the titer to BSA were found in the L line birds. During the first 3 wk of life, the linolenic acid-enriched diet resulted in reduced BW gain of H line birds. After that period, no effects of diet on BW gain was found. It is concluded that modulation of Ab responses of poultry to T cell-dependent antigens by essential fatty acids is affected by genotype. The relationship between magnitude of Ab responsiveness, BW, and essential fatty acids is discussed.

Topics: alpha-Linolenic Acid; Animals; Antibody Formation; Body Weight; Chickens; Dietary Fats, Unsaturated; Erythrocytes; Fatty Acids, Unsaturated; Female; Genotype; Linoleic Acid; Selection, Genetic; Serum Albumin, Bovine; Sheep; Weight Gain

Topics: alpha-Linolenic Acid; Arachidonic Acids; Body Height; Body Weight; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Erythrocyte Membrane; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Growth; Humans; Infant; Infant, Newborn; Linoleic Acid; Linoleic Acids; Male; Membrane Lipids; Phospholipids

Controlled feeding of linoleic acid (LA) or arachidonic acid (AA) to essential fatty acid-deficient (EFAD) rats was used to define the relationship between dietary AA and the inflammatory response evoked during adjuvant-induced arthritis. Based on energy percentage, EFAD rats were fed AA at the human daily equivalent (1x; 5.5 mg/day) or 10 times that amount (10x; 55 mg/day) or, alternatively 0.5x of LA (273 mg/day). Feeding of 0.5x LA restored the plasma level of AA to that in chow-fed controls. In contrast, feeding of 1x AA only partially restored the plasma level of AA; 10x AA was required to fully replete AA. In parallel to the degree of repletion of AA in plasma, there were accompanying decreases in the levels of palmitoleic acid, oleic acid, and Mead acid. Compared to rats fed the standard laboratory chow diet (Control), edema in the primary hind footpads was decreased by 87% in EFAD, 71% in EFAD + 1x AA, 45% in EFAD + 10x AA, and 30% in EFAD + 0.5x LA. The decrease in edema in the footpads of EFAD rats was nearly identical to the decrease in edema in the footpads of Control rats dosed with indomethacin. Hind footpad edema correlated with the final AA plasma level and eicosanoid levels extracted from hind footpad tissue, but not with neutrophil infiltration. The data showed that 0.5x LA and 10x AA, but not 1x AA, could quickly replete AA, accompanied by the synthesis of AA-derived eicosanoids and restoration of edema. These results suggest that in humans consumption of the average daily amount of AA without concurrent ingestion of LA would not alleviate an EFAD state.

Topics: Animals; Arachidonic Acid; Arthritis, Experimental; Body Weight; Dietary Fats; Disease Models, Animal; Eicosanoids; Energy Intake; Fatty Acids; Fatty Acids, Essential; Humans; Indomethacin; Linoleic Acid; Male; Neutrophils; Peroxidase; Rats; Rats, Inbred Lew; Time Factors

To investigate the involvement of (n-6) essential fatty acids, such as linoleic acid [18:2(n-6)] or gamma-linolenic acid [18:3(n-6)], and of prostaglandins on liver lipid accumulation in Japanese quail.. Effects of graded amounts of aspirin, which inhibits prostaglandin synthesis, on liver weight were determined in experiment 1. Experiment 2 was designed to clarify the effect of dietary essential fatty acid sources and inhibition of prostaglandin synthesis on the liver fat and fatty acid profile.. Female Japanese quail.. In experiment 1, from 1 to 3 weeks of age, birds were fed ad libitum the essential fatty acids-free or linoleic acid-adequate (2%) diets with graded amounts of aspirin (0, 0.1, 0.2, and 0.4%). In experiment 2, from 1 to 4 weeks of age, birds were fed the same amount of essential fatty acids-free, linoleic acid-adequate, or gamma-linolenic acid (0.4%) diets with (0.2%) or without aspirin.. In experiment 1, in groups given the essential fatty acids-free diet, liver weight increased with an increase in dietary aspirin concentration. In experiment 2, gamma-linolenic acid completely prevented liver triacylglycerol and cholesterol accumulation induced by the essential fatty acids-free diet. Aspirin treatment significantly lowered plasma prostaglandin F2 alpha concentration, but did not affect liver lipid concentrations. In groups fed the essential fatty acids-free diets, however, aspirin treatment increased liver weight and liver triacylglycerol concentration by 20 and 40%, respectively.. gamma-Linolenic acid or its metabolites, but not linoleic acid itself, are important factors in reducing fatty liver in Japanese quail with the essential fatty acids-deficient condition.

Topics: Animals; Aspirin; Body Weight; Coturnix; Dietary Fats; Dinoprost; Fatty Acids, Essential; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids; Lipid Metabolism; Liver; Organ Size; Prostaglandins

The relationship between dietary fat intake (level and type) and the development of breast cancer in humans is a matter of concern in Western society. A high fat intake is associated with a greater mammary cancer risk in humans and in animal models. Higher intake of polyunsaturated fatty acids in humans shows little or no association with mammary tumor development in epidemiologic surveys. From literature data, it appears that a higher intake of polyunsaturated fatty acids (linoleic acid) is related to an increase in mammary tumorigenesis in animal studies in which chemical carcinogens like dimethylbenz[a]anthracene are used as tumor initiator. Mostly the latency period of these chemically induced models in rather short. In this study, the Bald/c-MMTV (mouse mammary tumor virus) mouse strain was chosen as an animal model: MMTV leads to tumor initiation, and dietary factors influence tumor promotion over a relatively long latency period. The mice were fed diets with two fat concentrations: a high [36% of energy (en%)] or low (16 en%) fat level; fat was isocalorically replaced by carbohydrates (cornstarch). At both dietary fat levels, linoleic acid was given at four levels: 2, 3, 6, and 10 en%. Linoleic acid-rich fat was isocalorically replaced by oleic acid-rich fat. The diets were consumed ad libitum over a lifetime. Animals were euthanized as soon as mammary tumor diameter was > or = 1 cm or when the animals were in a poor clinical condition. The incidence of mammary tumors at 18 months was significantly higher in one group only: 36 en% fat and 2 en% linoleic acid. This group also showed the shortest mean latency period for mammary tumor development. Mean mammary tumor incidence was higher and mean onset time shorter in the four high-fat groups than in the low-fat groups. No (linear) dose-response relationship between dietary linoleic acid concentration and mammary tumor incidence and latency period was observed. This indicates that a higher dietary linoleic acid intake does not increase the incidence or shorten the latency period of breast cancer in the Balb/c-MMTV mouse strain at two different dietary fat levels.

Topics: Animals; Body Weight; Dietary Fats; Energy Intake; Female; Leukemia, Experimental; Linoleic Acid; Linoleic Acids; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice; Mice, Inbred BALB C

It has been suggested that low serum alpha tocopherol concentrations and a low proportion of polyunsaturated fatty acids in the serum cholesterol esters may be associated with a high risk of developing coronary heart disease.. In this study the intraindividual reproducibility (biological 'tracking') of these variables was studied in 855 men at the ages of 50 and 70 years.. The lipid adjusted tocopherol concentration was positively correlated (r = 0.28, P < 0.0001) between 50 and 70 years of age. Also the proportions of the serum cholesterol ester fatty acids were positively correlated between the same ages with r = 0.31 (P < 0.0001) for palmitic, r = 0.45 (P < 0.0001) for linoleic, and r = 0.58 (P < 0.0001) for arachidonic acid. The body weights of the men at 50 and 70 years of age were strongly correlated (r = 0.78, P < 0.0001).. The tocopherol concentrations and the fatty acid composition are related to vitamin intake and to the dietary fat quality, respectively, and may be useful markers in prospective studies of diseases and of development of diseases. The correlations between the proportions of fatty acids and the body weights, respectively at the ages of 50 and 70 indicate, that changes in diet and body weight in men are probably relatively limited between these years.

Topics: Aged; Arachidonic Acid; Body Mass Index; Body Weight; Cholesterol Esters; Fatty Acids; Follow-Up Studies; Humans; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Palmitic Acid; Vitamin E

The fatty acid derivative conjugated dienoic linoleate (CLA) has been shown to inhibit initiation and postinitiation stages of carcinogenesis in several experimental animal models. The goal of the present study was to determine the role of increasing levels of dietary CLA in mouse skin tumor promotion elicited by 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice were fed control (no CLA) diet during initiation, then switched to diets containing 0.0%, 0.5%, 1.0%, or 1.5% (wt/wt) CLA during skin tumor promotion by TPA. Body weights of mice fed 0.5%, 1.0%, or 1.5% CLA were similar to each other but were significantly lower (p < 0.05) than weights of mice fed no CLA (0.0%) throughout promotion. A reduction in papilloma incidence was observed in mice fed 1.5% CLA from Weeks 8 to 24 compared with mice fed diets containing 0.0-1.0% CLA (p < 0.05). Twenty-four weeks after tumor promotion was begun, diets containing 1.0% and 1.5% CLA inhibited tumor yield (4.94 and 4.35 tumors/mouse, respectively) compared with diets without CLA (0.0% CLA, 6.65 tumors/mouse, p < 0.05) or 0.5% CLA (5.92 tumors/mouse, p < 0.05). These data indicate that CLA inhibits tumor promotion in a manner that is independent of its anti-initiator activity. Further studies are warranted in identifying cellular mechanisms that are likely to be involved with the antipromoter effects of CLA.

Topics: Animals; Body Weight; Dietary Fats, Unsaturated; Female; Linoleic Acid; Linoleic Acids; Mice; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors

Spring-calving Brahman cows (S) artificially inseminated to Brahman, Angus, or Tuli sires and fall-calving Brahman cows (F) naturally bred to Brahman were allotted randomly to receive 3.74% (LF; n = 9 S and 6 F), 5.20% (MF; n = 8 S and 6 F), or 6.55% dietary fat (HF; n = 8 S). Diets were formulated to contain differing fatty acid concentrations and to be isocaloric and isonitrogenous. Cows were bled and fed twice daily from 2 wk before expected calving date through d 21 after calving. Ultrasonography was performed on d 14 and 21 after calving. From d 21 to 90 after calving a sterile bull equipped with a chin-ball marker was placed with the cows to aid in estrus detection. In both seasons progesterone decreased (P < .01) and estradiol-17 beta increased (P < .01) as parturition approached. Cows receiving MF and HF had increased (P < .01) total numbers of follicles compared to LF cows, and cows receiving MF had larger (P < .01) follicles. During the spring, cows receiving HF and cows bred to Brahman or Tuli sires had longer (P < .01) gestation lengths. Progesterone concentrations before calving were affected (P < .01) by treatment x sire and estradiol-17 beta by a time x treatment interaction (P < .01). Cholesterol after calving was higher (P < .01) in HF cows than in LF or MF cows. In the fall, LF cows had heavier (P < .01) calves than cows receiving MF. Birth weight was also affected (P < .01) by treatment x sex of calf. Progesterone was affected (P < .01) by treatment x sex of calf. Estradiol-17 beta was affected (P < .01) by sex of calf and treatment x sex of calf. Across seasons, by d 90 after calving, 9 of 15 (60%) LF and 11 of 15 (73.3%) MF cows showed estrual behavior. Cows in the spring had increased (P < .01) numbers and larger follicles compared to the fall. In conclusion, dietary fat may influence steroid hormone concentrations before calving, calf birth weight and postpartum follicular populations; furthermore, follicular populations may also be influenced by season.

Topics: Animals; Birth Weight; Body Weight; Cattle; Cholesterol; Dietary Fats; Estradiol; Female; Labor, Obstetric; Linoleic Acid; Linoleic Acids; Male; Oleic Acid; Ovarian Follicle; Postpartum Period; Pregnancy; Pregnancy Rate; Pregnancy, Animal; Progesterone; Random Allocation; Seasons; Sex Characteristics; Triglycerides

Studies were performed to determine whether feeding diets with differing fatty acid content and composition had an influence on systolic blood pressure in the rat. Weanling male rats were fed standard laboratory chow (2.9% fat in total), or synthetic diets (10% fat in total) containing fish oil, butter, coconut oil or corn oil, for 5 weeks. Coconut oil and butter diets were rich in saturated fatty acids, whilst fish oil and corn oil were rich in the n-3 and n-6 unsaturated fatty acids respectively. Systolic blood pressure was measured using an indirect tail-cuff method at the end of the feeding period, and compared to a group of weanling rats. Feeding the different diets did not alter the growth of the rats, so all animals were of similar weights at the time of blood pressure determination. Control (chow fed) animals, at nine weeks of age, had higher systolic blood pressures than the weanling, baseline control group. Fish oil fed rats had similar pressures to the chow fed rats. Corn oil fed rats had significantly lower systolic pressures than the controls. The rats led the diets rich in saturated fatty acids (butter and coconut oil) had significantly higher blood pressures than all other groups. Systolic blood pressure was found to be significantly related to the dietary intakes of saturated and unsaturated fatty acids. The dietary intake of linoleic acid was significantly higher in corn oil fed rats than in other groups. Systolic blood pressure was inversely related to linoleic acid intake. Feeding a diet rich in saturated fatty acids significantly increases blood pressure in the rat. A high intake of n-6 fatty acids, and in particular linoleic acid, appears to have a hypotensive effect. Prenatal exposure of the rats to a maternal low protein diet, abolished the hypertensive effects of the coconut oil diet and the hypotensive effect of the corn oil diet upon young adult females. The intrauterine environment may, therefore, be an important determinant of the effects of these fatty acids on blood pressure in later life.

Topics: Animals; Body Weight; Butter; Coconut Oil; Corn Oil; Dietary Fats; Dietary Fats, Unsaturated; Female; Fish Oils; Linoleic Acid; Linoleic Acids; Male; Plant Oils; Rats; Rats, Wistar; Reproducibility of Results; Systole

This study was designed to investigate polyunsaturated fatty acid (PUFA) biogenesis in spontaneously hypertensive rats (SHR) during the onset of hypertension. We measured liver desaturase activities, limiting enzymes of linoleic (LA) biosynthesis into arachidonic acid (AA). Fifteen male SHR and 15 male Wistar Kyoto (WKY) normotensive rats were killed at 7.9 or 13 week-old (5 per group). Systolic blood pressure was measured by plethysmography. Liver microsomes were obtained after ultracentrifugation and 5 mg of microsomal proteins incubated during 5 minutes at 37 degrees C with 0.04 mumoles of (1-14C) LA or (2-14C) dihomo-gamma-linolenic acid (DGLA). After fatty acid saponification and methylation, the bioconversion of (1-14C) LA into (1-14C) gamma-linolenic acid (GLA; delta 6 desaturation) and of (2-14C) DGLA into (2-14C) AA (delta 5 desaturation) was determined by measuring the radioactivity shared out between substrate and product of desaturation, after HPLC partition. Fatty acid composition of liver total lipids was calculated after GLC partition. In 7 week-old SHR, blood pressure was closed to that of WKY rats, higher in the 9 week-olds, when hypertension was settled in the 13 week-olds. Delta 6 and delta 5 desaturase activities were lower in SHR than in corresponding WKY. Those impaired desaturase activities increased with the age of rats: delta 6 desaturase activity was 43, 70 and 61% lower in the 7, 9 and 13 week-old SHR, respectively; delta 5 desaturase activity was 14, 48 and 53% lower in the same conditions. We observed a liver storage of total lipids in the 3 groups of SHR. The fatty acid composition of liver total lipids shows a lower proportion of AA and a higher proportion of LA in SHR than in WKY rats, confirming the depletion of the enzymatic systems studied. In summary, LA bioconversion into AA is decreased in liver microsomes of SHR, via the desaturase impairments. This phenomenon is concomitant with the pathogenesis of hypertension and related to the liver fatty acid composition. Such results explain partly the effects of PUFA rich diets administered to hypertensive rats, and clarify the interpretation of such effects.

Topics: Animals; Arachidonic Acid; Body Weight; Fatty Acid Desaturases; Fatty Acids, Unsaturated; Hypertension; Linoleic Acid; Linoleic Acids; Lipids; Male; Microsomes, Liver; Rats; Rats, Inbred SHR; Rats, Inbred WKY

It has been reported that gamma-linolenic acid (GLA)-rich diets suppress mammary carcinogenesis and transplanted tumor growth and that GLA inhibits the growth of cultured human cancer cell lines. We compared the effects of dietary GLA and linoleic acid (LA) on the growth of MDA-MB-435 human breast cancer cells and their expression of the metastatic phenotype in vivo and in vitro. Athymic nude mice (30/dietary group) were fed isocaloric diets containing 20% (wt/wt) fat but providing 8% GLA or LA for 7 days, and 10(6) tumor cells were then injected into a thoracic mammary fat pad. The diets were continued for a further 11 weeks. The primary tumor growth rates were similar in mice from the two dietary groups; there was a nonstatistically significant trend for the incidence of macroscopic lung metastases and the total lung metastatic volumes to be higher in the GLA-fed mice (79% and 40.1 +/- 13.9 mm3) than in the LA-fed mice (64% and 15.5 +/- 5.4 mm3). The tumor cell phospholipids from the 8% GLA-fed mice contained significantly lower LA levels but higher arachidonic acid levels (both p < 0.001) than those from 8% LA-fed mice. Also the arachidonate-derived eicosanoids (prostaglandin E, leukotriene B4, and 5-, 12-, and 15-hydroxyeicosatetraenoic acids) were significantly higher in tumors from the 8% GLA group. Zymography showed higher 92-kDa type IV collagenase activity in tumors from 8% GLA-fed mice. In vitro, GLA and LA, at 0.5-2 micrograms/ml, stimulated MDA-MB-435 cell growth; 10 micrograms/ml was mildly inhibitory. Whereas LA stimulated tumor cell invasion and 92-kDa type IV collagenase production in vitro, GLA inhibited invasion and did not induce activity of the proteolytic enzyme. Our results do not support the hypothesis that supplementation with GLA would exert a beneficial effect on the progression of an existing breast cancer, perhaps because it is metabolized in vivo to arachidonate-derived eicosanoids that are known to be involved in the metastatic process.

Topics: Animals; Arachidonic Acid; Body Weight; Breast Neoplasms; Cell Division; Collagenases; Dietary Fats; Eicosanoids; Fatty Acids; Female; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Invasiveness; Phospholipids; Tumor Cells, Cultured

Fatty acids in plasma phospholipids were studied in 35 severely malnourished young children with a median age of 29 mo (range: 9-43 mo), who were either seronegative for human immunodeficiency virus-1 (HIV) (n = 16) or suffered from asymptomatic (stage P-1; n = 12) or symptomatic (stage P-2; n = 7) HIV disease. The malnourished children had significantly lower percentages (% by wt) of phospholipid arachidonic (20:4n-6, AA) and docosahexaenoic (22:6n-3, DHA) acids than 25 age-matched healthy control subjects (AA: 7.05% and 8.70% by wt; DHA: 0.92 and 2.61% by wt, P < 0.001). Body weights of malnourished children did not correlate with linoleic (18:2n-6) and alpha-linolenic (18:3n-3) acid values but were significantly and positively correlated with AA and DHA values (r = 0.40, P = 0.02 and r = 0.63, P < 0.0001, respectively). Plasma concentrations (mg/L) of total phospholipid fatty acids did not differ among seronegative, stage P-1, or stage P-2 patients. Percentage contributions of AA and eicosapentaenoic acid (20:5n-3, EPA) did not differ among those seronegative or in stages P-1 and P-2. In contrast, values of dihomo-gamma-linolenic acid (20:3n-6) were significantly (P < 0.05) lower in stage P-2 (2.38 mg/L) than in either seronegative (3.47 mg/L) or stage P-1 (3.66 mg/L) patients. We conclude that the severely malnourished children developed a depletion of both AA and DHA proportional to the degree of malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arachidonic Acids; Body Weight; Child, Preschool; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; HIV Infections; HIV-1; Humans; Infant; Linoleic Acid; Linoleic Acids; Phospholipids; Protein-Energy Malnutrition

To make clear the mechanism of change of tryptophan-niacin metabolism in diabetic rats, we investigated the effect of dietary linoleic acid on the tryptophan-niacin metabolites and the activity of liver, alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), a key enzyme of tryptophan-niacin metabolism, in streptozotocin diabetic rats. Moreover, we investigated the involvement of linoleic acid in the induction of hepatic ACMSD activity by streptozotocin diabetes. In diabetic rats, the sum of urinary excretion of nicotinamide, N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py) and N1-methyl-4-pyridone-3-carboxamide (4-Py) was higher in the fat free diet group than in the linoleic acid group, that was accompanied by the increase of tryptophan intake and reduction of body weight in the fat free diet group. In diabetic rats, hepatic ACMSD activity was higher in the fat free diet group than in the linoleic acid group. The results indicated that the induction of hepatic ACMSD activity by diabetes was not due to removal of the suppressive effect of the linoleic acid on the enzyme. In the diabetic+insulin group, hepatic ACMSD activity was significantly lower than in the diabetic group.

Topics: Animals; Body Weight; Diabetes Mellitus, Experimental; Diet; Eating; Linoleic Acid; Linoleic Acids; Male; Niacin; Niacinamide; Rats; Rats, Sprague-Dawley; Tryptophan

In rats, the response of adipose tissue composition to a single weight cycle (24-48 h of fasting followed by refeeding) is characterized by a decrease primarily in linoleate and alpha-linolenate, with little or no change in other fatty acids. We tested the hypothesis that during successive weight cycles caused by repeated fasting and refeeding, the depletion of linoleate and alpha-linolenate from whole body stores would be exacerbated despite their adequate availability during the refeeding period. Four complete weight cycles (24-h fasting followed by 72-h ad libitum refeeding) induced a significant quantitative decrease in total n-3 and n-6 polyunsaturates, particularly linoleate and alpha-linolenate, and a simultaneous increase in the accumulation of palmitate, palmitoleate, and oleate in carcass total lipids and in perirenal and epididymal adipose tissue. A significant positive relationship was observed between the increasing ratio of saturates+monounsaturates to n-3 + n-6 polyunsaturates in adipose tissue and the number of weight cycles (r = +0.96, P < 0.0001). The percentage of linoleate and alpha-linolenate in adipose tissue was inversely related to the number of weight cycles. We conclude that, despite providing adequate n-6 and n-3 polyunsaturates in the diet during the refeeding period, weight cycling in young growing rats causes a moderate, selective depletion of linoleate and alpha-linolenate from tissue stores.

Topics: Adipose Tissue; alpha-Linolenic Acid; Animal Feed; Animals; Blood; Body Weight; Fasting; Fatty Acids; Linoleic Acid; Linoleic Acids; Liver; Male; Organ Size; Rats; Rats, Sprague-Dawley

The effect of long-term sucrose intake on lipid metabolism and milk composition was examined in lactating mice and correlated with the development of their pups. Female mice were weaned onto semi-purified diets containing 685 g starch or sucrose/kg diet. Food intake was similar on the two diets. At mid-lactation, milk was collected and analysed. Milk from sucrose-fed dams had a lower percentage of linoleic acid (18:2n-6) and a higher percentage of oleic acid (18:1n-9), although milk fat content was similar. Hepatic fatty acid synthesis (as measured by 3H2O incorporation into fatty acid) was three times faster in sucrose-fed than in starch-fed dams. Dietary carbohydrate had no effect on fatty acid synthesis or functional lipoprotein lipase (EC 3.1.1.34) activity in mammary gland, nor on plasma triacylglycerol concentration. Pups from first litters were killed at 11-12 d and body composition analysed. Pups born to sucrose-fed dams were significantly heavier with increased body fat and higher levels of plasma glucose and triacylglycerol. Litters of sucrose- and starch-fed dams were cross-fostered at birth and killed at 10-12 d. Analysis of variance indicated that maternal sucrose intake, both during pregnancy and lactation, increased body fat of offspring. The increases in body weight and plasma triacylglycerol of preweaning offspring were caused primarily by maternal sucrose intake during lactation.

Topics: Animals; Animals, Newborn; Blood Glucose; Body Composition; Body Weight; Dietary Carbohydrates; Fatty Acids; Female; Lactation; Linoleic Acid; Linoleic Acids; Lipid Metabolism; Liver; Mice; Mice, Inbred BALB C; Milk; Oleic Acid; Oleic Acids; Pregnancy; Prenatal Exposure Delayed Effects; Starch; Sucrose; Triglycerides

Three different groups of infants were fed with different formulae based on milk fat. Group I received cow's milk fat formulae with 20% butter fat whereas groups II and III received a formulae which was supplemented with 50 and 33% of peanut oil supplementation in 20% milk fat respectively. Anthropometric measurements, cholesterol, triglyceride, lipoproteins and plasma fatty acids were followed up to a period of 6 months. The results indicated that cow's milk-fed infants had higher cholesterol levels (P < 0.01) than the other two groups. No significant differences with respect to high-density lipoproteins (HDLs) were found, whereas low-density lipoproteins (LDLs) and very low-density lipoproteins (VLDls (VLDls) were found to be increasing up to a period of 6 months. No significant differences were observed with respect to saturated fatty acids and oleic acid (18:1) levels whereas linoleic acid (18:2) clearly showed a proportional relationship between the intake and plasma levels, indicating a positive correlation. Arachidonic acid (20:4) did not, however, show a proprotionate relationship with respect to linoleic acid (18:2) intake. The triene/tetraene, oleic/linoleic, linoleic/arachidonic and total n6 fatty acids were all normal indicating normal activity of desaturase and elongase enzymes for the optimal utilisation of linoleic acid. Thus, the present study suggests that a vegetable oil such as peanut oil could be used in milk fat to improve the essential fatty acid (EFA) status of infants.

Topics: Animals; Arachidonic Acid; Body Height; Body Weight; Cohort Studies; Fatty Acids; Follow-Up Studies; Food, Fortified; Humans; Infant Food; Infant Nutritional Physiological Phenomena; Infant, Newborn; Linoleic Acid; Linoleic Acids; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Milk; Oleic Acid; Oleic Acids; Peanut Oil; Plant Oils

The effect of very low levels of dietary long-chain n-3 fatty acids on delta 6 desaturation of linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), and on delta 5 desaturation of dihomo-gamma-linolenic acid (20:3n-6), in liver microsomes and its influence on tissue fatty acids were examined in obese and lean Zucker rats and in Wistar rats. Animals fed for 12 wk a balanced diet containing ca. 200 mg of long-chain polyunsaturated n-3 fatty acids per 100 g of diet were compared to those fed the same amount of alpha-linolenic acid. Low amounts of long-chain n-3 fatty acids greatly inhibited delta 6 desaturation of 18:2n-6 and delta 5 desaturation of 20:3n-6, while delta 6 desaturation of 18:3n-3 was not inhibited in Zucker rats and was even stimulated in Wistar rats. Inhibition of the biosynthesis of long-chain n-6 fatty acids was reflected in a decrease in arachidonic acid (20:4n-6) content of serum lipids when fasting, and also in the phospholipid fatty acids of liver microsomes. On the contrary, heart and kidney phospholipids did not develop any decrease in 20:4n-6 during fish oil ingestion. Docosahexaenoic acid (22:6n-3), present in the dietary fish oil, was increased in serum lipids and in liver microsome, heart, and kidney phospholipids.

Topics: Animals; Body Weight; Dietary Fats; Docosahexaenoic Acids; Fatty Acids; Fish Oils; Kidney; Linoleic Acid; Linoleic Acids; Liver; Male; Microsomes, Liver; Myocardium; Organ Size; Rats; Rats, Wistar; Rats, Zucker; Species Specificity

1. The importance of linoleic acid (18:2n-6) itself and of dietary gamma-linolenic acid (18:3n-6) as essential fatty acids (EFA) in Japanese quail were investigated with regard to liver lipid metabolism. Experimental diets were made by adding of 0, 2 or 4 g gamma-linolenic acid/kg, or 20 g linoleic acid/kg to an n-6 EFA-free diet. From 3 to 6 weeks of age, birds were fed equal amounts of experimental diets. 2. Liver weight and lipid content in birds fed the 2 and 4 g gamma-linolenic acid/kg diet were significantly lower than those in birds fed the gamma-linolenic acid-free diet. However, no significant difference was observed between the gamma-linolenic acid- and linoleic acid-supplemented diets. 3. In birds fed the 4 g gamma-linolenic acid/kg diet, the proportion of arachidonic acid in the liver lipid was similar to that in quail fed the 20 g linoleic acid/kg diet, implying a conversion rate from linoleic acid to gamma-linolenic acid of approximately 20% of whole body content. 4. It is concluded that linoleic acid itself is not essential for Japanese quail and that at least 2 g/kg of gamma-linolenic acid in the diet completely prevents liver enlargement accompanied by lipid accumulation.

Topics: Analysis of Variance; Animals; Body Weight; Chromatography, Gas; Coturnix; Dietary Fats, Unsaturated; Fatty Acids; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids; Lipid Metabolism; Lipids; Liver; Organ Size; Safflower Oil; Weight Gain

Pregnancy-induced changes in whole-body partitioning of linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) between accumulation, conversion to longer-chain polyunsaturates (LCP), and disappearance (apparent oxidation) were determined over a 13-day balance period. 18:2n-6, 18:3n-3 and n-6 and n-3 LCP levels were measured in food, feces, organs, and carcass. Accumulation was estimated on the basis of paired difference values between one group killed at the beginning and one at the end of the balance period. Actual whole-body accumulation of 18:2n-6 and 18:3n-3 (mg per rat) was similar in pregnant and nonpregnant rats, but when expressed as milligrams per gram weight gain, it was greater in nonpregnant rats. Net accumulation of n-6 and n-3 LCP was significantly greater in pregnant rats whether expressed as milligrams per rat or as milligrams per gram body weight gain. Apparent oxidation of 18:2n-6 and 18:3n-3 expressed as a percentage of intake was similar in both groups, but when expressed as milligrams per gram weight gained, it was significantly greater in the nonpregnant group. We conclude that the balance method provides a useful index of whole-body and organ partitioning of 18:2n-6 and 18:3n-3. This method demonstrates that despite the higher accumulation of LCP during pregnancy, significantly more 18:2n-6 and 18:3n-3 is apparently oxidized than is converted to their respective LCP.

Topics: alpha-Linolenic Acid; Animals; Body Weight; Eating; Female; Linoleic Acid; Linoleic Acids; Organ Size; Oxidation-Reduction; Pregnancy; Pregnancy, Animal; Rats; Rats, Sprague-Dawley

The aim of this work was to study the effect of dietary n - 6 (as borage oil) and of n - 3 (as fish oil) fatty acids on the incorporation--in liver microsomal lipid classes--of fatty acids involved in delta 6- and delta 5-desaturations in obese Zucker rats compared with their lean littermates and with Wistar control rats. We observed that body and liver weights were decreased when obese Zucker rats were fed the fish oil diet. The major part of the radioactivity was recovered, in the obese Zucker rats, into the neutral lipids and especially into the triacylglycerols, while it was recovered into the phospholipid classes, especially into phosphatidylcholine, in the two other strains. Results show, in all phenotypes, an increased alpha-linolenic acid delta 6-desaturation in PL classes when the rats were fed the fish oil diet. However, a decreased linoleic acid delta 6- and delta 5-desaturation was observed in obese Zucker rats fed the fish oil diet. The fish oil diet favours the n - 3 fatty acid biosynthesis and incorporation into liver microsomal lipid classes to the prejudice of the n - 6 fatty acid series. The fatty acid incorporation is simultaneously regulated by the genetical phenotype and dietary fatty acids.

Topics: alpha-Linolenic Acid; Animals; Body Weight; Delta-5 Fatty Acid Desaturase; Dietary Fats, Unsaturated; Fatty Acid Desaturases; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Linoleic Acid; Linoleic Acids; Linoleoyl-CoA Desaturase; Liver; Male; Microsomes, Liver; Obesity; Organ Size; Rats; Rats, Wistar; Rats, Zucker; Triglycerides

In the present study the modulating effects of dietary fish oil (MaxEPA) on unsaturated fat-promoted pancreatic carcinogenesis in azaserine-treated rats were investigated. Three groups of 20 rats (each group comprised five saline-treated and 15 azaserine-treated animals) were fed an AIN76-based purified diet containing (i) 5 wt% fat, (ii) 25 wt% fat including 5 wt% linoleic acid or (iii) 25 wt% fat including 5 wt% linoleic acid and 9.4 wt% (20 cal%) MaxEPA for 6 months. The number and size of pancreatic atypical acinar cell foci was significantly higher (P < 0.01) in azaserine-treated animals maintained on a high fat diet than in those fed a low fat diet. MaxEPA did not influence the promoting effect of the high fat diet. The labeling index of atypical acinar cell foci in animals maintained on both a low fat or a high fat/MaxEPA diet was significantly (P < 0.01) lower than that in rats fed a high fat diet without MaxEPA. The linoleic acid concentration was higher, whereas the arachidonic acid concentration was lower, in blood plasma and to a lesser extent also in the pancreas of animals given MaxEPA in comparison with the other groups. Furthermore, animals fed MaxEPA showed lower 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha and thromboxane B2 levels, but not prostaglandin E2 levels in pancreatic tissue in comparison with the other groups. It is concluded that a high fat diet containing 5 wt% linoleic acid has a strong promoting effect on pancreatic carcinogenesis in azaserine-treated rats. Dietary MaxEPA did not influence the promoting effect of unsaturated fat on pancreatic carcinogenesis, although it caused a decrease in both cell proliferation in atypical acinar cell foci and prostaglandin levels in the pancreas.

Topics: Animals; Anticarcinogenic Agents; Azaserine; Body Weight; Cell Division; Dietary Fats; Eating; Fatty Acids; Fish Oils; Linoleic Acid; Linoleic Acids; Male; Organ Size; Pancreas; Pancreatic Neoplasms; Precancerous Conditions; Prostaglandins; Rats; Rats, Wistar

Obese Zucker rats (fa/fa) have low levels of arachidonic acid (AA) in liver phospholipids (PL). We have previously shown that a 70% gamma-linolenate concentrate (GLA; an AA intermediate) fed at a fixed dose (0.07 g/day) normalized hepatic PL AA and reduced weight gain selectively in the obese animals. In a follow-up study, 16 obese (fa/fa) and 16 lean (Fa/Fa) 4-week-old male rats were randomized into 4 groups of 8 each and gavaged daily with soybean oil (SOY) containing 55% 18:2omega6 (an AA precursor) or GLA, using a progressive dose (< or = 5% of total calories) based on body weight. A defined diet with 11% of energy as SOY was fed ad libitum for 60 days. GLA obese had lower body weight (p<0.0001) and 60-day cumulative food intake (p<0.05) compared to SOY obese, but neither parameter differed between the lean groups. For the last twenty days cumulative food intake was identical for GLA obese and SOY lean, whereas SOY obese consumed 18% more (p<0.05). Thus the progressive dose of GLA selectively suppressed hyperphagia in obese Zucker rats. Erythrocytes collected at 15-day intervals showed parallel increases in AA in both genotypes over time, suggesting normal AA availability during rapid growth. Thus, the reduced PL AA in the livers from the obese rats probably reflects impaired distribution in selected tissues rather than reduced hepatic production. Due to the potential health risks of enriching tissue lipids with AA, great caution is advised in considering GLA as therapy for human obesity.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Body Composition; Body Weight; Dietary Supplements; Disease Models, Animal; Eating; Energy Metabolism; Erythrocytes; Fatty Acids; gamma-Linolenic Acid; Genotype; Glycine max; Growth; Hyperphagia; Linoleic Acid; Lipid Metabolism; Lipids; Liver; Male; Obesity; Phospholipids; Rats; Rats, Zucker; Time Factors; Weight Gain

Ingested polyunsaturated fatty acids are postulated to lead to changes in central nervous system activity, presumably by altering the lipid composition of neuronal membranes. In support of this hypothesis, we and other investigators have previously demonstrated cognitive effects in rats fed oils that contain both alpha-linolenic acid (18:3 omega 3) and linoleic acid (18:2 omega 6), with the relative content of alpha-linolenic acid being seen as the critical variable. The present study in rats examined the effects of preparations containing different ratios of highly purified free alpha-linolenic acid to linoleic acid (about 25 mg/kg of body weight daily) on learning performance (Morris water tank), pain thresholds (heated plate), and thermoregulatory control of d-amphetamine-induced hypothermia during 4 weeks of treatment. Preparations with omega 3-to-omega 6 ratios ranging from 1:3.5 to 1:5 (specifically a ratio of 1:4) produced significant favorable effects on all of these variables. Although the specific mode of action remains to be elucidated, these results suggest that such preparations of free fatty acids should be evaluated in the treatment of memory disorders and pain conditions.

Topics: alpha-Linolenic Acid; Animals; Body Temperature Regulation; Body Weight; Dietary Fats; Energy Intake; Feeding Behavior; Learning; Linoleic Acid; Linoleic Acids; Male; Motor Activity; Pain; Rats; Sensory Thresholds

To study the influence of membrane fatty acid composition on the formation of prostanoids and hydroxy fatty acids by rat peritoneal mast cells (MC), animals were fed three different types of fatty acids: mackerel oil (MO), abundant in n-3 fatty acids; sunflower seed oil (SO), rich in linoleic acid; and hydrogenated coconut oil (HCO), mainly containing saturated fatty acids. The presence of n-3 fatty acids in the diet resulted in the incorporation of 20:5(n-3), 22:5(n-3) and 22:6(n-3) in MC phospholipids. A decrease of arachidonic acid, 20:4(n-6), was observed in MC-phospholipids of the MO-fed animals. Furthermore, increasing the relative amounts of 18:2(n-6) in the diet (SO group) led to an increased incorporation of linoleic acid, 18:2(n-6) in MC phospholipids when compared to both other dietary groups. The changes in MC phospholipid fatty acid composition were (partly) reflected in the formation of prostanoids and hydroxy fatty acids upon stimulation with the calcium ionophore A23187. The decrease in arachidonic acid content in MC phospholipids of MO-fed rats resulted in a decreased formation of PGD2 when compared to both other groups. Also, the increased amounts of 18:2(n-6) in MC phospholipids of SO-fed rats resulted in an increased formation of 9- and 13-HODE upon stimulation. The results show that modifications in the fatty acid composition of the diet influences MC membrane fatty acid composition which ultimately results in changes in prostanoid and hydroxy fatty acid synthesis by MC upon stimulation with the calcium ionophore A23187.

Topics: Animals; Arachidonic Acid; Body Weight; Calcimycin; Cell Membrane; Coconut Oil; Dietary Fats; Fatty Acids; Fish Oils; Linoleic Acid; Linoleic Acids; Male; Mast Cells; Peritoneal Cavity; Phospholipids; Plant Oils; Prostaglandins; Rats; Rats, Wistar; Sunflower Oil

Age-related changes in delta 6 desaturation of [1-14C]alpha-linolenic acid and [1-14C]linoleic acid and in delta 5 desaturation of [2-14C]dihomo-gamma-linolenic acid were studied in liver microsomes from Wistar male rats at various ages ranging from 1.5 to 24 mon. Desaturase activities were expressed both as specific activity of liver microsomes and as the capacity of whole liver to desaturate by taking into account the total amount of liver microsomal protein. delta 6 Desaturation of alpha-linolenic acid increased from 1.5 to 3 mon and then decreased linearly up to 24 mon to reach the same desaturation capacity of liver measured at 1.5 mon. The capacity of liver to desaturate linoleic acid increased up to 6 mon and then remained constant, whereas microsomal specific activity was equal at 1.5 and 24 mon of age. The capacity of liver to convert dihomo-gamma-linolenic acid to arachidonic acid by delta 5 desaturation decreased markedly from 1.5 to 3 mon. It then increased to reach, at 24 mon, the same level as that observed at 1.5 mon. Age-related changes in the fatty acid composition of liver microsomal phospholipids at the seven time points studied and of erythrocyte lipids at 1.5 and 24 mon were consistent with the variations in desaturation capacity of liver. In particular, arachidonic acid content in old rats was slightly higher than in young rats whereas contents in linoleic and docosahexaenoic acids varied little throughout the life span.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 8,11,14-Eicosatrienoic Acid; Aging; Animals; Arachidonic Acid; Body Weight; Delta-5 Fatty Acid Desaturase; Fatty Acid Desaturases; Fatty Acids; Fatty Acids, Unsaturated; Linoleic Acid; Linoleic Acids; Linoleoyl-CoA Desaturase; Liver; Male; Microsomes, Liver; Organ Size; Phospholipids; Rats

Oral administration of eicosapentaenoic acid (EPA) (2.0 g/kg) by gavage to female NMRI mice bearing the MAC16 colon adenocarcinoma and with weight loss, prevented further loss in body weight and produced a delay in the growth of the tumour. Cell production and loss were determined by the [125I]5-iodo-2'-deoxyuridine method during the stationary and growth phase of the tumour in animals treated with EPA. Tumour stasis appeared to arise from an increase in the rate of cell loss from 38 to 71% without a significant change in the potential doubling time. During the subsequent growth phase the cell loss factor was reduced to 52% and this was combined with a reduced potential doubling time from 32 to 26 hr. The antiproliferative, but not the anticachectic effect of EPA could be reversed by oral administration of pure linoleic acid (LA), (1.9 g/kg) which acted to increase tumour growth by reducing the cell loss factor to 45%. Despite this reversal, incorporation of EPA into tumour cell lipids was not significantly different in animals administered with either EPA alone or combined with LA. This suggests that the antiproliferative effect of EPA in this system may arise from an indirect effect through the blocking of the catabolic effect of the tumour on host adipose tissue, which normally supplies fatty acids essential for tumour growth. This suggests that LA may be required by some tumours to prevent cell loss and that the catabolism of adipose tissue, which accompanies cancer cachexia effectively supplies this fatty acid to the tumour.

Topics: Adenocarcinoma; Animals; Body Weight; Cell Cycle; Colonic Neoplasms; Eicosapentaenoic Acid; Fatty Acids; Female; Linoleic Acid; Linoleic Acids; Lipids; Mice; Tumor Cells, Cultured

Both alpha-tocopherol and a 1:1.7 mixture of alpha-tocopherol and tocotrienols at a 0.2% dietary level significantly depressed the age-related increase in the systolic blood pressure of spontaneously hypertensive rats (SHRs) after 3 weeks of feeding. The aortic production of prostacyclin was increased 1.5 times both by alpha-tocopherol and a tocotrienol mixture, suggesting a possible relevance to their hypotensive effect. These vitamins did not influence the delta 6- and delta 5-desaturase activities of liver microsomes, but fatty acid profiles of the liver phospholipids predicted a reduction of linoleic acid desaturation. These effects were in general more clear with tocotrienols than with alpha-tocopherol. Platelet aggregation by 5 microM ADP remained uninfluenced. Thus, tocotrienols may have effects on various lipid parameters somewhat different from those of alpha-tocopherol.

Topics: Animals; Aorta, Thoracic; Arachidonic Acid; Blood Pressure; Body Weight; Delta-5 Fatty Acid Desaturase; Epoprostenol; Fatty Acid Desaturases; Fatty Acids; Linoleic Acid; Linoleic Acids; Linoleoyl-CoA Desaturase; Lipids; Liver; Male; Microsomes, Liver; Phosphatidylcholines; Platelet Aggregation; Rats; Rats, Inbred SHR; Vitamin E

Rats with essential fatty acid deficiency (EFAD) exhibit mild body growth retardation, diminished leukocyte influx in certain models of inflammation, and skin lesions characterized by ulceration, thinning and decreased pigmentation. In the present study we examined the role of EFAD in cutaneous wound healing, a process in which the inflammatory response and the macrophage play a central role. We reproduced the EFAD condition in Lewis rats (n = 35), and examined its effects in wound healing using the paired rat surgical incision model. Rats were compared with weight-matched controls, receiving standard chow diet. Skin samples harvested at days 5, 7, 14 and 21 post-wounding were evaluated for tensiometry and histology. EFAD rats exhibited all the characteristics of this condition, and the typical alteration of liver lipids. Skin samples harvested at different days post-wounding did not show difference in maximal breaking strength when compared to weight-matched controls. Histological evaluation of skin samples showed no difference in the cellular inflammatory infiltration in either EFAD rats or in weight-matched controls. Immunohistochemical studies revealed no difference in the influx of macrophages in the different groups of rats. Fatty acid supplementation of EFAD rats (n = 7), successfully reversed the EFAD state as assessed by the macroscopic skin and liver changes and liver fatty acid content, without modifying either tensile strength or cellular inflammatory infiltration. Our results suggest that EFAD does not alter the normal course of the cutaneous wound repair in rats, despite all the cutaneous alterations produced by this condition. We conclude that essential fatty acids (EFAs) are not essential for cutaneous wound repair.

Topics: Animals; Body Weight; Dietary Fats, Unsaturated; Fatty Acids, Essential; Inflammation; Linoleic Acid; Linoleic Acids; Macrophages; Male; Rats; Rats, Inbred Lew; Skin; Tensile Strength; Wound Healing

The effects of dietary pantethine levels on the contents and compositions of fatty acids and on the levels of lipid peroxides were investigated with rat liver and its S-9 fraction under administration of 0 (non), 0.2 (low dose), and 0.35 ml (high dose) of autoxidized linoleate (AL) per 100 g body weight of the rats per day for 5 days. AL having 800 meq/kg of peroxide value (PV) and 1,700 meq/kg of carbonyl value (CV) was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25 mg% (adequate), and 125 mg% pantethine (excess). In the pantethine-deficient and -adequate groups, the contents of fatty acids both in the liver homogenate and in the S-9 fraction were correspondingly decreased by increasing dose levels of AL, and the decrease was remarkable especially in the pantethine-deficient group, but was not significant in the pantethine-excess group even by a high dose of AL. Particularly, in the high dose of AL, the notable decreases of oleic acid (C18:1) contents in both the liver and the S-9 fraction were observed in rats of the pantethine-deficient and -adequate groups. The thiobarbituric acid (TBA) values in the liver homogenate and the S-9 fraction were increased correspondingly by increasing dose levels of AL, and the increases were repressed in the pantethine-excess group.

Topics: Administration, Oral; Animals; Body Weight; Chromatography, Gas; Fatty Acids; In Vitro Techniques; Linoleic Acid; Linoleic Acids; Liver; Male; Malondialdehyde; Pantetheine; Rats; Rats, Inbred Strains; Thiobarbiturates

Oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL. The initial step in the oxidation is the peroxidation of polyunsaturated fatty acids. Thus, decreasing the concentration of polyunsaturated fatty acids should reduce the susceptibility of LDL to oxidation. Therefore, we tested the possibility that diets enriched in oleate might result in LDL that is less susceptible to oxidative modification. LDL isolated from subjects consuming an oleate-enriched diet, compared with LDL from subjects on a linoleate-enriched diet, contained significantly more oleate (28.7% vs 11.5%) and less linoleate (31.9% vs 50.9%). Generation of conjugated dienes was significantly lower in the LDL from the oleate group. Most important, after incubation with endothelial cells, LDL from the oleate group underwent less degradation by macrophages. These studies demonstrate the feasibility of altering the diet in a way that will not raise LDL cholesterol concentrations and yet will decrease the susceptibility of LDL to oxidative modification.

Topics: Adult; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet Records; Dietary Fats, Unsaturated; Fatty Acids; Helianthus; Humans; Linoleic Acid; Linoleic Acids; Lipid Peroxidation; Lipoproteins, LDL; Oleic Acids; Oxidation-Reduction; Patient Compliance; Plant Oils; Random Allocation; Sunflower Oil

Based on the biological activity of arachidonic acid metabolites, we hypothesized that alterations in the consumption of linoleic acid, the precursor to arachidonic acid, would result in a modification in tumor development when fed during the tumor promotion stage of the mouse skin initiation-promotion model. The effects of seven different levels of dietary linoleic acid (LA), supplied as corn oil in a 15% fat diet, on the incidence and rate of papilloma and carcinoma development were determined. SENCAR mice were placed on one of the experimental diets, containing 1.0, 3.6, 6.0, 7.9, 9.9, 12.5, or 15.0% corn oil, 1 week after initiation with 10 nmol of 7,12-dimethylbenz(a)anthracene and 3 weeks prior to the start of twice weekly promotion with 1 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA). At 15 weeks of TPA treatment there were significant differences in papilloma number among diet groups, such that an inverse correlation (r = 0.92) was observed between tumor number and level of corn oil; the lowest corn oil diet group had an average of 11.7 tumors/mouse, while the highest corn oil group had 5.4 tumors/mouse. However, there was little difference in tumor incidence among diet groups. A general relationship between diet and carcinoma incidence was also found, such that the highest corn oil diet group had the lowest carcinoma incidence. In an experiment performed with DBA/2 mice, the average number of papillomas/mouse at 17 weeks was 4.5 (1.0% corn oil), 5.6 (7.9%) corn oil), and 2.3 (15.0% corn oil). Papilloma incidence was also affected by diet, with a 79% incidence for the 15.0% corn oil and an incidence of 93% for the 1.0% corn oil group. analyses of the fatty acid composition of epidermal phospholipids in mice fed the experimental diets reflected the dietary LA levels, in that an accumulation of phospholipid LA, accompanied by an overall decrease in arachidonic acid, occurred with increasing dietary corn oil. In spite of the high membrane levels of LA, no measurable amount of epidermal conjugated dienes of LA could be detected. Epidermal prostaglandin E2 levels in acetone-treated mice were similar for all diet groups (approximately 3 pg/micrograms DNA). However, 6 h after topical application with 4 micrograms of TPA, prostaglandin E2 levels were elevated 5- to 10-fold; an inverse correlation (P less than 0.05) was seen with increasing dietary LA, although the concordance with decreased phospholipid arachidonic acid was not strong.(ABSTRACT TR

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Body Weight; Carcinoma; Corn Oil; Dinoprostone; Female; Linoleic Acid; Linoleic Acids; Mice; Mice, Inbred DBA; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate

Metabolism of octadecadienoic acid isomers in weanling mice was studied by feeding fat-free diets supplemented with 2% by weight of cis-9,trans-12-octadecadienoic acid (c,t-18:2-d0), tetradeuterated trans-9,cis-12-octadecadienoic acid (t,c-18:2-d4) or dideuterated cis-9,cis-12-octadecadienoic acid (c,c-18:2-d2). Rates for conversion of c,t-18:2-d0 and c,c-18:2-d2 to c,t-20:4-d0 and c,c-20:4-d2 were identical and both were 5-times higher than conversion of t,c-18:2-d4 to t,c-20:4-d4. Accumulation of t,c-18:2-d4 in liver lipids was 2-4-times higher than for c,t-18:2-d0 or c,c-18:2-d2. The t,c-18:2 diet significantly increased with the 20:3(n-9) and total lipid concentrations in liver but not in heart, plasma or brain. The 20:3(n-9)/20:4(n-6) ratio in the liver lipids was 2-4-times higher for t,c-18:2-d4 than c,c-18:2-d2 fed mice. The position of the trans bond had a marked influence on the distribution of the various intermediate desaturation and elongation products. Intermediate metabolite data for the liver lipids indicated t,c-18:2-d4 was preferentially converted to 5c,11c,14t-20:3 ('dead end' product) rather than to t,c-20:4. Concentration of the 18:3(n-6) metabolite of c,t-18:2-d0 was about 10-times greater than the 18:3(n-6) metabolite of c,c-18:2-d2. Conversely, the concentration of the normal 20:3(n-6) metabolite from c,c-18:2-d2 was 4-times higher than the 20:3(n-6) metabolite of c,t-18:2-d0. Compared to the c,c-18:2 diet, the t,c- and c,t-18:2 diets significantly increased the total n-3, but not the total n-6 fatty acid content of heart lipids. These results illustrate that the position of the trans double-bond influences a variety of enzyme activities and the isomers differ in their physiological effects.

Topics: Animals; Body Weight; Brain Chemistry; Chromatography, Gas; Fatty Acids; Linoleic Acid; Linoleic Acids; Liver; Male; Mice; Myocardium; Stereoisomerism

Serum lipid profiles, serum immunoglobulins, and serum proteins were investigated in 65 noninstitutionalized older women living in a rural community. All women were mentally and physically able to participate in the study. They did not have any overt disease nor were they taking any prescription or nonprescription drugs that would interfere with the study. Personal interview elicited medical history, drug usage, dietary information, height, and weight from 25 reference women (50 through 64 years old), 28 young-old women (65 through 84 years old), and 12 old-old women (85 through 92 years old). Blood samples were obtained from fasting participants and analyzed for total serum cholesterol, high-density-lipoprotein cholesterol, serum triglyceride, serum immunoglobulins (IgG, IgA, and IgM), serum albumin, and total serum protein. Serum lipids were not significantly affected by age, drug use, or age-by-drug use interaction. Effects of age were observed for IgA and serum albumin. Mean concentrations of serum immunoglobulins, serum albumin, and total serum proteins were within normal limits for all participants. Based on this small sample of rural older women, our results indicate that the normal levels of high-density-lipoprotein cholesterol and the healthy life-styles of these women may help offset any possible negative effects of elevated serum cholesterol concentrations.

Topics: Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Blood Proteins; Body Height; Body Weight; Cholesterol; Cholesterol, Dietary; Diet; Dietary Fats; Energy Intake; Fatty Acids; Female; Humans; Immunoglobulins; Iowa; Linoleic Acid; Linoleic Acids; Lipids; Middle Aged; Pharmaceutical Preparations; Rural Population; Triglycerides; Vitamin E; Zinc

We measured the subcutaneous adipose tissue fatty acid composition in 22 male Ethiopian Jews, aged 17-65, shortly after their immigration to Israel. These subjects showed a concentration of linoleic acid (17.8%), which was relatively low compared with Israeli levels, and a high concentration of palmitic acid (28.5%). The linoleic/saturated (P/S) ratio was 0.52. After 5 months, a repeat measurement indicated increases of the linoleic acid content and of the P/S ratio to 20.1% and 0.62, respectively (P less than 0.05). In another sample from the same immigrant group, levels after 1 year in Israel were 20.9% and 25.1% for linoleic and palmitic acid, respectively, and the P/S ratio was 0.67. These results differed significantly (P less than 0.02) from those obtained in the first sample after immigration. Apart from decreasing plasma triglyceride levels, no pattern of lipid changes was discernible in our limited samples. Changes in subcutaneous fatty acid composition reflect changes in diet over months, suggesting a decreased carbohydrate intake and in increased fat intake. It remains to be seen whether changing fatty acid composition in conjunction with changes in blood lipids or other factors, over a prolonged period of time, will affect the cardiovascular risk in the immigrants.

Topics: Adipose Tissue; Adolescent; Adult; Aged; Body Composition; Body Mass Index; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Ethiopia; Humans; Israel; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Palmitic Acid; Palmitic Acids; Prospective Studies; Triglycerides

Interpretation of studies comparing the efficacy of different dietary fat sources in promoting 7,12-dimethylbenz[a]-anthracene (DMBA)-induced rat mammary tumorigenesis often ignores the fact that about 4% (wt/wt) linoleic acid (18:2n-6) is required for optimal tumor promotion. We therefore fed DMBA-intubated or placebo-intubated female, Sprague-Dawley rats 20% fat diets containing 18:2n-6 (wt/wt) from either high-linoleic safflower oil (SL, 14.6% 18:2n-6), high-oleic safflower oil (SO, 3.4% 18:2n-6), olive oil (OO, 1.1% 18:2n-6), or OO supplemented with 18:2n-6 (OL, 3.4% 18:2n-6) for 16 weeks. Results indicated that OO-fed rats had longer tumor-free time, fewer tumors per rat, and lower tumor incidence compared with SO and OL. Addition of 2.3% 18:2n-6 to OO enhanced tumor promotion (p less than 0.04); SL, SO, and OL demonstrated similar tumor-enhancement effect. About 74% of observed mammary tumors were adenocarcinomas; a greater number of tumors appeared in the thoracic and inguinal than in the cervical and abdominal regions irrespective of diet. These results indicate that once an optimal amount of linoleic acid is provided in the diet, oleic- or linoleic-rich oils have similar effects on promotion of mammary tumors in the rat.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Animals; Body Weight; Carcinogens; Dietary Fats, Unsaturated; Female; Insulin-Like Growth Factor I; Linoleic Acid; Linoleic Acids; Liver; Mammary Neoplasms, Experimental; Olive Oil; Organ Size; Plant Oils; Rats; Rats, Inbred Strains; Safflower Oil; Spleen

There were no statistically significant differences in final body weight or in food intake among groups of rats fed for 7 wk various fats of animal origin (lard fat and cod liver oil) or vegetable origin (corn, soybean and canola oils); the fats were fed as 10% of the diet (by wt) and were of varied fatty acid composition. Nevertheless, the mean weights of the kidneys from cod liver oil-fed animals were significantly higher than those of all other dietary groups. Platelets of rats from the groups receiving the animal fat contained significantly lower levels of linoleic acid, 18:2(n-6) [a precursor of arachidonic acid, 20:4(n-6)], than did platelets from rats receiving the fat of vegetable origin. Although the soybean-, canola- and cod liver oil-fed animals received substantial quantities of (n-3) fatty acids [alpha-linolenic acid, 18:3(n-3); eicosapentaenoic acid, 20:5(n-3); and docosahexaenoic acid, 22:6(n-3)], only the platelets of the latter two groups contained detectable levels of these fatty acids along with their products of elongation/desaturation/retroconversion. Platelets of the cod liver oil-fed group contained significantly less arachidonic acid, a major precursor of eicosanoids, than did those from all other dietary groups. However, platelet arachidonic levels also varied markedly among the other dietary groups. Diet-induced fatty acid changes observed in platelets of various dietary groups may influence platelet responses, including secretion, aggregation and biosynthesis of eicosanoids.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Body Weight; Chromatography, Gas; Cod Liver Oil; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Fish Oils; Linoleic Acid; Linoleic Acids; Male; Organ Size; Plant Oils; Rats; Rats, Inbred Strains

[3H]arachidonic acid (20:4) and [14C]linoleic acid (18:2) were fed in a triolein emulsion to essential fatty acid-deficient (EFAD) rats and to age-matched controls. Tissues were analyzed for radioactivity of different lipid classes after 1, 2, and 4 h. As in earlier studies [Nilsson and Melin. Am. J. Physiol. 255 (Gastrointest. Liver Physiol. 19): G612-G618, 1988], control rats retained more [3H]20:4 than [14C]18:2 in all organs except adipose tissue. In EFAD rats, recovery of [14C]18:2 was increased in small intestine, liver, heart, and kidneys. In comparison to controls, EFAD rats retained much more [14C]18:2 in phospholipids of these organs. The increase in the incorporation of both 3H and 14C into phosphatidylethanolamine was particularly pronounced. Another striking feature was the drastic increase in the retention after 4 h of 14C in cardiolipin, which is specifically located in the inner mitochondrial membrane. In contrast, incorporation of both 3H and 14C into phosphatidylinositol was decreased or unchanged in EFAD rats. Although fecal fat excretion was increased there was no evidence for a malabsorption or an increased retention in intestinal triacyglycerol of the radioactive fatty acids in EFAD rats. The proportion of [14C]18:2 that had been converted to [14C]20:4 was generally low but increased significantly with time in the liver and intestine of EFAD rats.

Topics: Aging; Animals; Arachidonic Acid; Arachidonic Acids; Body Weight; Carbon Radioisotopes; Fatty Acids; Fatty Acids, Essential; Female; Intestinal Absorption; Intestinal Mucosa; Intestines; Linoleic Acid; Linoleic Acids; Maternal-Fetal Exchange; Organ Specificity; Phospholipids; Pregnancy; Radioisotope Dilution Technique; Rats; Rats, Inbred Strains; Reference Values; Tritium

We studied linoleic acid delta 5 and dihomo-gamma-linolenic acid delta 5 desaturations, and fatty acid composition, of liver microsomes in the insulin-dependent spontaneously diabetic adult female BB rat. These desaturations were defective along the normo- and hyper-glycemic period and restored during the hypoglycemic period which followed the insulin injection to the diabetic rats. The fatty acid composition of BB rats microsomes was not consistent with the desaturase activities at the different periods of glycemia, probably because other factors than desaturation impairments were involved in the evolution of fatty acid composition.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Blood Glucose; Body Weight; Delta-5 Fatty Acid Desaturase; Diabetes Mellitus, Experimental; Fatty Acid Desaturases; Female; Insulin; Linoleic Acid; Linoleic Acids; Linoleoyl-CoA Desaturase; Microsomes, Liver; Organ Size; Rats; Rats, Inbred BB; Rats, Inbred Strains

Dietary fat has been shown to enhance pancreatic carcinogenesis. Uncertainty still exists whether the amount of linoleic acid or the amount of fat is the main determining factor. In the present study the effects of a high lard, a low lard, a linoleic acid supplemented low lard and a laboratory chow diet were investigated on the development of (pre)neoplastic pancreatic lesions in rats treated with azaserine. The rats were killed 15 months after carcinogen treatment and the pancreata were examined for the number and size of putative preneoplastic lesions and for the occurrence of neoplasms. The linoleic acid supplemented low lard group showed a significantly increased number of basophilic foci as compared to the low lard group. Rats maintained on the linoleic acid supplemented diet or the laboratory chow developed significantly less atypical acinar cell nodules larger than 1.0 mm in diameter and adenocarcinomas as compared to the high lard group. Animals maintained on the low lard diet developed significantly less adenocarcinomas than rats on the high lard diet did. Overall, the number of benign and malignant pancreatic tumours was consistently higher in the high lard group and consistently lower in the linoleic acid supplemented low lard group than the number of these types of tumours in the low lard group, with the exception of the number of carcinomas in situ, which was lower in the high lard group. The laboratory chow group showed a significant lower number of atypical acinar cell nodules with a diameter over 1.0 mm and a lower number of adenocarcinomas as compared to both the high lard and the low lard group. It is concluded that a diet high in saturated fat has a promoting and that laboratory chow has an inhibitory effect on pancreatic carcinogenesis in azaserine-treated rats.

Topics: Animals; Azaserine; Body Weight; Diet; Dietary Fats; Eating; Incidence; Linoleic Acid; Linoleic Acids; Liver; Male; Organ Size; Pancreas; Pancreatic Neoplasms; Rats; Rats, Inbred Strains

Essential fatty acid (EFA) deficiency exerts a striking protective effect in several animal models of autoimmune disease. We now report that EFA deprivation prevents diabetes in the BB rat, an animal model of human insulin-dependent diabetes mellitus. In diabetes-prone (DP)-BB rats, the incidences of spontaneous diabetes and insulitis (the pathological substrate of autoimmune diabetes) were greatly reduced by EFA deficiency. This beneficial effect of the deficiency state was also seen in diabetes-resistant (DR)-BB rats that, after treatment with antibody to eliminate RT6+ T cells, would otherwise have become diabetic. The susceptibility of EFA-deprived DP-BB rats to spontaneous diabetes was restored when they were given dietary supplements of linoleate at 70 d of age (during the usual period of susceptibility), but not when they were repleted beginning at 120 d (after the peak incidence of diabetes). EFA deficiency did lead to growth retardation, but calorically restricted control rats demonstrated that the protective effect of the deficiency state was not a function of decreased weight. To examine the relationship between the biochemical changes of EFA deficiency and its physiological effects in this system, we compared the fatty acid changes that occurred in EFA-deficient animals that did and did not develop diabetes. Nondiabetic animals had significantly lower levels of (n-6) fatty acids (i.e., linoleate and arachidonate) and higher levels of oleate, an (n-9) fatty acid, than did diabetic animals. Levels of 20:3(n-9), the fatty acid that uniquely characterizes EFA deficiency, were similar in both groups, however. Among diabetic EFA-deficient rats, the age at onset of diabetes was found to correlate inversely with the level of (n-6) fatty acids, the least depleted animals becoming diabetic earliest, whereas there was no correlation with levels of 20:3(n-9). Among animals repleted with linoleate beginning at 70 d, restoration of susceptibility to diabetes correlated with normalization of the level of arachidonate. In summary, EFA deprivation reduced the frequency of diabetes in both DP and RT6-depleted DR-BB rats. This protective effect was strongly associated with depletion of (n-6) fatty acids, particularly arachidonate, but not with accumulation of the abnormal 20:3(n-9). Conjecturally, arachidonate and/or a metabolite may play a key role in mediating inflammatory injury in this animal model of autoimmune diabetes.

Topics: Animals; Autoimmune Diseases; Body Weight; Diabetes Mellitus, Experimental; Fatty Acids; Fatty Acids, Essential; Female; Linoleic Acid; Linoleic Acids; Macrophages; Male; Rats; Rats, Inbred BB

This study examines whether oleate may influence the linoleate enhanced metastasis of line 4526 murine mammary tumors. In addition, the in vitro proliferative response of line 4526 to oleate and other selected fatty acids was assessed. Initially, the tumor cells were grown in a defined medium supplemented with palmitate, stearate, oleate, linoleate, linolenate or arachidonate. The unsaturated fatty acids stimulated and the saturated fatty acids inhibited proliferation compared to fatty acid-free medium. Next, we examined the effect of oleate on the linoleate enhanced metastasis of 4526 tumors by substituting oleate for saturated fat in isoenergetic diets containing high or low levels of linoleate. Oleate had no effect on metastasis in mice fed the high linoleate diets but it significantly increased metastasis in mice fed the low linoleate diets. Finally, the fatty acid compositions of tumors and mammary fat pads were compared to diet fatty acid compositions and metastatic frequency. Metastasis corresponded more closely to total unsaturated fatty acids than to total polyunsaturated fatty acids or to any individual fatty acid. These studies suggest that both mono- and polyunsaturated fatty acids may stimulate mammary tumor metastasis. However, the influence of dietary oleate probably depends on the level of linoleate and total unsaturated fatty acids in the diet.

Topics: Animals; Body Weight; Cell Division; Dietary Fats, Unsaturated; Dose-Response Relationship, Drug; Fatty Acids; Female; Linoleic Acid; Linoleic Acids; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Oleic Acid; Oleic Acids; Organ Size; Tumor Cells, Cultured

Several studies have shown that the development of high blood pressure in spontaneously hypertensive rats (SHR) can be attenuated by feeding them modified fat diets. In the present study, eight weeks after treatment with eicosapentaenoic acid (EPA; 100 mg/kg/day s.c.) SHR had lower systolic blood pressure (BP); (tail-cuff plethysmography) compared to saline-injected SHR: 180.0 +/- 2 vs. 204.0 +/- 1 mmHg, respectively, (p less than 0.001). There was no significant difference in the BP of EPA and saline-treated WKY (Wistar-Kyoto) rats. Heart rate (HR) decreased with age in both the SHR and WKY rats and no significant effect of EPA was observed in WKY rats; the decrease in heart rate in the SHR group was significantly diminished. EPA did not significantly alter growth rate of SHR and WKY rats. However, aged-matched WKY rats weighed more than the SHR. The pressor responses to norepinephrine in doses of 0.3 and 3.0 microgram/kg, i.v., as well as plasma NE, DOPA and MHPG, were also not significantly affected by EPA-supplementation in both SHR and WKY rats. Data from the present study support the view that EPA might be an effective treatment of hypertension that develops via mechanisms unrelated to sympathetic activity or vascular reactivity to adrenergic neurotransmitters.

Topics: Animals; Blood Pressure; Body Weight; Cardiovascular System; Dicarboxylic Acids; Dihydroxyphenylalanine; Eicosapentaenoic Acid; Heart Rate; Hemodynamics; Hypertension; Linoleic Acid; Linoleic Acids; Male; Methoxyhydroxyphenylglycol; Norepinephrine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors

Rats were fed diets containing a high level of saturated fatty acids (hydrogenated beef tallow) versus a high level of linoleic acid (safflower oil) at both low and high levels of fish oil containing 7.5% (w/w) eicosapentaenoic and 2.5% (w/w) docosahexaenoic acids for a period of 28 days. The effect of feeding these diets on the cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding diets high in fish oil with safflower oil decreased the cholesterol content of rat serum, whereas feeding fish oil had no significant effect on the cholesterol content of serum when fed in combination with saturated fatty acids. The serum cholesterol level was higher in animals fed safflower oil compared to animals fed saturated fat without fish oil. Consumption of fish oil lowered the cholesterol content of liver tissue regardless of the dietary fat fed. Feeding diets containing fish oil reduced the arachidonic acid content of rat serum and liver lipid fractions, the decrease being more pronounced when fish oil was fed in combination with hydrogenated beef tallow than with safflower oil. These results suggest that dietary n-3 fatty acids of fish oil interact with dietary linoleic acid and saturated fatty acids differently to modulate enzymes of cholesterol and fatty acid metabolism.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Body Weight; Cholesterol; Dietary Fats; Docosahexaenoic Acids; Eating; Eicosapentaenoic Acid; Fatty Acids; Fish Oils; Linoleic Acid; Linoleic Acids; Lipid Metabolism; Lipids; Liver; Male; Organ Size; Rats; Rats, Inbred Strains

To investigate whether dietary linoleic acid inhibits lymphocyte proliferation, rabbits were fed diets containing 35% of the digestible energy (35 en%) as sunflower seed oil (25 en% linoleic acid) or palm oil (3.5 en% linoleic acid). No differences in the mitogen-induced proliferation of peripheral blood lymphocytes (PBL) or splenocytes or in the effect of sera on PBL proliferation were observed. To investigate whether the amount of dietary fat affects lymphocyte proliferation, rats were fed diets containing 10 or 35 en% as fat. No difference in the mitogen-induced proliferation of splenocytes was obtained. However, serum from fed rats but not from fasted rats of the 35 en% fat group inhibited splenocyte proliferation, in comparison with serum from rats of the 10 en% fat group. Removing chylomicrons from the sera did not affect proliferation. The very low density lipoprotein + chylomicron fraction of the plasma inhibited proliferation. The inhibition was stronger for the 35 en% fat group than for the 10 en% fat group and was increased by fasting. No systematic differences in the effects on proliferation were obtained with the low or high density lipoprotein fractions of both groups. Diets containing a high amount of linoleic acid do not inhibit lymphocyte proliferation. The amount of dietary fat might affect lymphocyte proliferation through one or more factors in the plasma.

Topics: Animals; Body Weight; Cells, Cultured; Dietary Fats; Leukocyte Count; Linoleic Acid; Linoleic Acids; Lipoproteins; Lymphocyte Activation; Male; Rabbits; Rats; Rats, Inbred Strains; Spleen; T-Lymphocytes

Rats were fed a diet either deficient (0.05%) in essential fatty acids (EFA), or providing 4% (control) and 10% (surplus) of the total energy intake in the form of linoleic acid. All diets were isoenergetic and provided 13.9% of the energy as fat. The rats were kept at 29 or 5 degrees C. Growth and food intake of rats fed linoleic acid surplus at either temperature for 10 wk were not different from that of controls; basal metabolism, norepinephrine-induced nonshivering thermogenesis (NST) and thermogenic variables in the brown adipose tissue (amount of mitochondria and mitochondrial uncoupling protein) also were not different. The effects of EFA deficiency were drastically enhanced in the cold: After 10 wk of consuming a diet low in EFA at 5 degrees C, the body weight of rats was 75% of that of controls (87% at 29 degrees C); the food intake was 135% of controls at 5 degrees C (120% at 29 degrees C). The resting respiration in deficient rats was 125% of controls at 5 degrees C (110% at 29 degrees C); body temperatures as low as 35.1 degrees C were measured in deficient rats after 3 wk at 5 degrees C; the cold tolerance of the rats was significantly diminished (30% died within 3 wk at 5 degrees C), thus emphasizing the essential role of dietary EFA during cold stress. Norepinephrine-induced NST and the thermogenic parameters in brown fat were not influenced by EFA deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Cold Temperature; Dietary Fats; Energy Metabolism; Fatty Acids, Essential; Linoleic Acid; Linoleic Acids; Male; Oxygen Consumption; Rats; Rats, Inbred Strains

Selenium is an essential component of glutathione peroxidase, which reduces free and esterified hydroperoxides of polyunsaturated fatty acids. Adequate glutathione peroxidase activity could be important for the maintenance of prostacyclin synthesis by blood vessels, since hydroperoxides can inhibit the formation of this substance. We have investigated the effects of dietary selenium deficiency on glutathione peroxidase activity and the synthesis of 6-oxoprostaglandin F1 alpha and monohydroxy and trihydroxy metabolites of polyunsaturated fatty acids by aorta. The latter products can be formed either by the actions of cyclooxygenase or lipoxygenase or by lipid peroxidation. Aortic glutathione peroxidase activity was reduced by over 80% by feeding rats a selenium-deficient diet for 4 weeks, and to undetectable levels after 6 weeks. There were no appreciable differences in the levels of free and esterified oxygenated metabolites of linoleic acid or arachidonic acid between the control and treated groups after 4 weeks. However, after 6 weeks, there were modest, but statistically significant reductions in the formation of 6-oxoprostaglandin F1 alpha and monohydroxy products formed by cyclooxygenase. On the other hand, the amounts of esterified 18:2 metabolites appeared to be higher in aortae from animals on the selenium-deficient diet, although only the increase in esterified 9-hydroxy-10,12-octadecadienoic acid was statistically significant. These results suggest that selenium deficiency can affect the formation of prostacyclin and other oxygenated metabolites of polyunsaturated fatty acids by aorta, possibly by increasing lipid peroxidation. However, the differences between control and selenium-deficient rats after 6 weeks were not very dramatic, in spite of the fact that glutathione peroxidase activity was undetectable. It would therefore appear that additional mechanisms are also involved in controlling the levels of lipid hydroperoxides in aorta.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Arachidonic Acid; Arachidonic Acids; Body Weight; Dinoprostone; Esterification; Fatty Acids, Unsaturated; Glutathione Peroxidase; Linoleic Acid; Linoleic Acids; Lipid Peroxides; Lipoxygenase; Male; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Rabbits; Rats; Rats, Inbred Strains; Selenium

Vitamin E and linoleate, both of which are found in high concentrations in sunflower seed oil, were examined independently for their influence on general and blood-vascular parameters in vitamin E-deficient common marmosets. A vitamin E-deficient diet (-E, 4 micrograms/g) was supplemented with either 40 micrograms/g vitamin E (+E), vitamin E stripped sunflower oil (+10% SSO-E), or SSO (+10% SSO w/w) in a 2 x 2 factorial designed experiment, and the diets fed for 9 months to 4 even groups of common marmosets. Vitamin E deficiency was associated in marmosets with a loss of skeletal muscle mass and of body weight, enhanced peroxidative haemolysis of erythrocytes, increased white blood cell counts, and in the SSO-E group a relative neutrophilia. Platelet reactivity was increased with vitamin E deficiency, and to a greater degree with the SSO-E group. Aortic prostacyclin production was significantly increased by the addition of vitamin E, linoleate and both as SSO to the deficient diet, the effects being additive. Fatty acid changes associated with the different treatments reflected the influence of high linoleate and vitamin E treatments. The platelet and aortic arachidonate value in the SSO-E group showed the lowest and most variable value, and this was associated with greatest platelet aggregability. An adequate vitamin E intake is essential for stabilising high PUFA diets and biomembranes and enhancing the protective role of prostacyclin in blood vessels against thrombogenesis.

Topics: Animals; Aorta; Blood Platelets; Body Weight; Callithrix; Dietary Fats, Unsaturated; Fatty Acids; Female; Hemolysis; Leukocyte Count; Linoleic Acid; Linoleic Acids; Lipid Peroxides; Muscles; Organ Size; Plant Oils; Platelet Aggregation; Prostaglandins; Prostaglandins F; Sunflower Oil; Thromboxane B2; Vitamin E; Vitamin E Deficiency

Autoxidized linoleic acid (AL) having 800 meq/kg of peroxide value and 1,700 meq/kg of carbonyl value was given in repeated oral doses for 1-15 days at a daily dose of 2.5 ml/kg to male Wistar rats. During the administration, the effect of AL on drug-metabolizing activity was investigated periodically in liver microsomes. The contents of cytochrome P-450 and b5 were increased by consecutive oral doses for 3-7 days. Thereafter, the amount of cytochrome P-450 decreased gradually, but the b5 decreased slightly. Thus, after administration for 11-15 days, the cytochrome P-450 content was significantly lower but the cytochrome b5 content was rather high in comparison with the control group. The aminopyrine-N-demethylase activity was not reduced even after repeated oral doses of AL for 15 days. The activation of 2-acetyl amino fluorene (2-AAF), which the authors termed S-9 activity, gradually decreased during administration for more than 3 days, and completely disappeared after administration for 9 days.

Topics: 2-Acetylaminofluorene; Aminopyrine N-Demethylase; Animals; Body Weight; Cytochrome b Group; Cytochrome P-450 Enzyme System; Cytochromes b5; Linoleic Acid; Linoleic Acids; Liver; Male; Microsomes, Liver; Organ Size; Oxidation-Reduction; Pharmaceutical Preparations; Rats; Rats, Inbred Strains

Investigations on diet, body weight, and lipoproteins were carried out in 28 patients with stable angina pectoris. They consumed a linoleic acid-enriched diet (P/S ratio = 2) for a period of 2 years. The total fat content remained constant before and during intervention, contributing 34% to energy intake. During intervention serum total cholesterol and the total/HDL cholesterol ratio decreased significantly, but HDL cholesterol did not change. Changes in body weight were significantly inversely related to changes in HDL cholesterol and positively to the total/HDL cholesterol ratio. Changes in alcohol intake were significantly positively related to both total and HDL cholesterol but unrelated to the total/HDL cholesterol ratio. From the results of this long-term study it can be concluded that a moderate fat diet with a P/S ratio of 2 can lower total cholesterol effectively without affecting HDL cholesterol.

Topics: Adult; Alcohol Drinking; Angina Pectoris; Body Weight; Cholesterol; Cholesterol Esters; Cholesterol, HDL; Diet; Fatty Acids; Female; Humans; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Time Factors

Female rats with 1-3/4 nephrectomy were divided in two groups and pair fed for five weeks diets differing in their linoleic acid content. Five weeks after subtotal nephrectomy, values for glomerular filtration rate and renal plasma flow were significantly higher and the values of blood pressure significantly lower in rats fed a diet rich in linoleic acid. Systolic blood pressure averaged 156 +/- 5.6 mm Hg in high and 215 +/- 8.1 mm Hg in low linoleic acid-fed rats. Differences in the values of blood pressure between the two groups were observed three weeks after subtotal renal ablation and persisted throughout the period of observation. Inulin clearance averaged 0.89 +/- 0.07 ml/min in the high and 0.44 +/- 0.05 ml/min in the low linoleic acid group. Protein excretion in the urine was significantly less in rats fed the high linoleic acid diet (36.9 +/- 4.4 mg/24 hr) than in those fed the low linoleic acid diet (90.1 +/- 12.5 mg/24 hr). The weight of the remnant kidney five weeks after subtotal renal ablation was greater in rats fed a low linoleic acid diet as compared to those fed a high linoleic acid diet (P less than 0.05). Glomerular lesions were more severe in rats fed a low linoleic acid diet than in those fed a high linoleic acid diet. Feeding high linoleic acid diets to normal and subtotally nephrectomized rats increased the content of linoleic and arachidonic acid in renal cortex and medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Body Weight; Dietary Fats; Fatty Acids; Female; Inulin; Kidney; Kidney Function Tests; Linoleic Acid; Linoleic Acids; Nephrectomy; p-Aminohippuric Acid; Prostaglandins; Proteinuria; Rats; Rats, Inbred Strains

The influence of quantitative differences in dietary linoleic acid (18:2) on the metastasis as well as the development of line 4526 mouse mammary tumors was investigated. High fat diets (20%, w/w) that contained either 1, 2, 4, 8, or 12% 18:2 by weight, were prepared by using mixtures of coconut and safflower oil and fed to female BALB/c mice that were subsequently inoculated with 10(4) 4526 tumor cells s.c., either at the lateral abdominal wall (LAW) or in the mammary fat pad (MFP). Latency of LAW tumors was influenced by the level of dietary 18:2, whereas the latency of MFP tumors was not. When metastasis was assessed, mice with MFP tumors fed 1, 2, 4, or 8% 18:2 diets had 62-73% fewer lung surface tumor nodules than similar mice fed 12% 18:2. Mice in all dietary groups with LAW tumors had fewer metastatic lung nodules than mice with MFP tumors; mice with LAW tumors fed diets containing 1, 2, or 4% 18:2 had 52-69% fewer nodules than similar mice fed diets containing 8 or 12% 18:2. There were no significant differences in the rate of increase of body weight or the daily mean tumor volumes when compared with dietary 18:2 level. Fatty acid composition of the tumor, particularly the level of 18:2, was significantly altered by diet. This study demonstrates that while the level of dietary 18:2 does not enhance the growth rate of primary 4526 tumors and does or does not affect the latency depending on the primary site, it does significantly alter the metastasis. These results stress the importance of metastasis assessment in future studies involving dietary fat effects on tumorigenesis.

Topics: Animals; Body Weight; Dietary Fats; Fatty Acids; Female; Linoleic Acid; Linoleic Acids; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neoplasm Transplantation

A low protein diet affects amounts of linoleic and arachidonic acids in hepatic microsomal phospholipids of growing rats. Are the changes related to modifications in microsomal delta 6- and delta 5- linoleic acid desaturase activities? Two groups of Wistar rats weighing 80 +/- 5 g at the beginning of the experiment were used: Control group (T) was fed on a 16% gluten + 4% casein diet for 53 days; Experimental group (E) was fed on a 4% gluten + 1% casein diet for 26 days (MP) then Control diet for 27 days (RE). After 2, 14 and 26 days of MP and 2, 15 and 27 days of RE, rats of each group were sacrificed. Protein and water contents of liver, quantitative fatty acid, composition of total lipids in liver and hepatic microsomes were determined. delta 6- and delta 5- linoleic acid desaturase activities were estimated from incubation of liver microsomes with [1-14C] C 18: 2 n-6 or [2(14)C] C 20: 3 n-6 respectively. The low protein diet stops practically ponderal growth. The fatty-acid compositions of microsomal total lipids of E rats were affected in comparison with values of T rats. These modifications persist after 27 days of RE. The C 20: 4 n-6/C 18: 2 n-6 ratio in microsomal total lipids was slightly different between T and E rats but increased strongly during refeeding. Same modifications take place in the fatty-acid composition of hepatic total lipids. After two days of MP, delta 6- and delta 5- desaturase activities were depressed, phenomenon that not persist in the course of MP. These enzyme activities increase to higher values than those of the T after two days of RE.

Topics: Animals; Body Weight; Delta-5 Fatty Acid Desaturase; Dietary Proteins; Fatty Acid Desaturases; Linoleic Acid; Linoleic Acids; Linoleoyl-CoA Desaturase; Male; Microsomes, Liver; Organ Size; Rats; Rats, Inbred Strains

The polyunsaturated-saturated (P/S) fatty acid, and linoleic-linolenic (18:2n6/18:3n3) acid ratios of diets fed to rats were varied independently during pregnancy, lactation and, in the young, for 8 d after premature weaning. The intent was to alter the proportion of membrane phospholipid fatty acids derived from 18:2n6 and 18:3n3 in the developing rat, and to compare changes in very-long-chain polyunsaturated fatty acids in membranes from the central nervous system with those of the red blood cell. All experimental diets contained 40% of energy from fat. Similar relative changes in phosphatidylethanolamine (PE) and phosphatidylcholine (PC) fatty acid pattern occurred in both neural and red blood cell membranes when dietary 18:2n6/18:3n3 was increased from 7 to 240. Docosapentaenoate (22:5n6) from 18:2n6 increased, and docosapentaenoate (22:5n3) and docosahexaenoate (22:6n3) from 18:3n3 decreased in both types of membranes. On the other hand, P/S ratios of 0.3 and 1.6 at a constant ratio of 18:2n6/18:3n3 produced identical membrane phospholipid fatty acid patterns. Both red blood cell and neural membranes show the same relative effects of modification of dietary lipids on the composition of very-long-chain polyunsaturated fatty acids.

Topics: alpha-Linolenic Acid; Animals; Body Weight; Brain; Cell Membrane; Dietary Fats; Erythrocytes; Fatty Acids; Fatty Acids, Unsaturated; Female; Glucose; Injections, Intraperitoneal; Linoleic Acid; Linoleic Acids; Linolenic Acids; Maternal-Fetal Exchange; Organ Size; Phospholipids; Pregnancy; Rats; Rats, Inbred Strains

The effects of different types of dietary lipids were tested in burned guinea pigs. All diets were identical except for the type of lipid, with total energy intake from lipids equaling 10%. All animals received a 30% total body surface area (TBSA) flame burn and were fed identically by pump-controlled gastrostomy feedings for 14 days. When compared to safflower oil (74% linoleic acid) as well as linoleic acid alone, fish oil (18% eicosapentaenoic acid or EPA) administration resulted in less weight loss, better skeletal muscle mass, lower resting metabolic expenditure, better cell mediated immune responses, better opsonic indices, higher splenic weight, lower adrenal weight, higher serum transferrin, and lower serum C3 levels. With the exception of better cell mediated immune responses in the animals fed linoleic acid, the administration of indomethacin made little difference. These findings can be explained by a reduction in the synthesis of the dienoic prostaglandins that are derived from the omega 6 series of fatty acids, some of which are significantly immunosuppressive. Regulation of dietary lipids may be an important therapeutic advance in nutritional support after burn injury, and controlled trials should be considered.

Topics: Animals; Body Weight; Burns; Complement C3; Dietary Fats; Dinoprostone; Eicosapentaenoic Acid; Energy Metabolism; Female; Guinea Pigs; Immunity, Cellular; Indomethacin; Linoleic Acid; Linoleic Acids; Macrophages; Nitrogen; Organ Size; Phagocytosis; Prostaglandins E; Transferrin

The effect of total parenteral nutrition (TPN) with lipid emulsions containing ca. 48% 18:2 omega 6 plus 8% 18:3 omega 3 (Intralipid) or 76% 18:2 omega 6 plus 0.5% 18:3 omega 3 (Liposyn) on the fatty acid composition of liver and plasma triglyceride and phospholipid (PL) was studied in the rat. Plasma PL showed a clear influence of the egg PL present in the infused lipid, suggesting replacement of endogenous lipoprotein PL. The incorporation of 20 and 22 carbon omega 6 and omega 3 fatty acids was reduced in liver phosphatidylcholine of rats infused with either Intralipid or Liposyn. Phosphatidylethanolamine was much less affected and showed reduced 20:4 omega 6 and 20:5 omega 3 in the Liposyn group only. Reduction in levels of long chain essential fatty acid metabolites was compensated for by an increased content of saturated fatty acids. There was no accumulation of 18:2 omega 6 or 18:3 omega 3 in liver PL. The similarity between the effects of Intralipid and Liposyn supports the conclusion that 18:2 omega 6, not 18:3 omega 3, was responsible. The data suggest that intravenous administration of high levels of 18:2 omega 6 in parenteral lipid reduces desaturation/elongation of essential fatty acids but does not competitively inhibit esterification of other fatty acids into PL.

Topics: Animals; Body Weight; Emulsions; Fatty Acids, Unsaturated; Linoleic Acid; Linoleic Acids; Lipids; Liver; Male; Parenteral Nutrition, Total; Phosphatidylcholines; Phospholipids; Rats; Rats, Inbred Strains; Triglycerides

A reduction in the size of transplantable mammary adenocarcinoma IX was achieved when female BALB/c mice were fed isocaloric 10% fat diets containing either hydrogenated cottonseed oil (HCTO) or menhaden oil (MO) as opposed to those mice fed corn oil (CO). Indeed, CO increased the size of the neoplasms when fed alone at 5 or 1% of the diet, although such diets contained less fat calories than did the 10% fat diets containing the other two oils. At the 10% level of dietary fat, enhanced accumulation of tumor mass was observed even when 7.5, 5.0, and 2.5% CO was administered in combination with either HCTO or MO. Although this effect of CO could not be inhibited when nine times as much HCTO was added to the diet, such growth enhancement was abolished when the diet contained nine times as much MO. Hence these experiments emphasized the importance of the type rather than the amount of dietary fat. Whereas MO contained polyunsaturated fatty acids (PUFA's) [approximately 1% as linoleic acid, approximately 16% as 5,8,11,14,17-eicosapentaenoic acid (EPA), approximately 11% as 4,7,10,13,16,19-docosahexaenoic acid (DHA)], HCTO contained none and CO had about 60% of its constituent fatty acids in the form of linoleic acid. The rate of tumor cell loss, determined by the [125I]5-iodo-2'-deoxyuridine method, in the 10% MO-fed or the 10% HCTO-fed mice (54 or 45%, respectively) was more than twice that observed for tumors from the 10% CO-fed mice (22%). These observations were discussed in terms of the influence of the dietary PUFA linoleic acid [C 18:2 (No. of carbons:No. of double bonds), n-6], the PUFA EPA (C 20:5, n-3), and the PUFA DHA (C 22:6, n-3) on the size of mammary tumors and on the involvement of prostaglandins in this process.

Topics: Adenocarcinoma; Animals; Body Weight; Corn Oil; Cottonseed Oil; Dietary Fats; Fatty Acids; Female; Fish Oils; Linoleic Acid; Linoleic Acids; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Oils; Prostaglandins

Rats of an inbred Sprague-Dawley strain were fed purified diets with low (0.3% of total energy), normal (3%) or high (10%) content of essential fatty acids (EFA) for at least three generations. Two 30-day-old rats with similar weights were chosen from one litter. One was killed; weight increase and food consumption of the other rat was measured for 15 days. Total lipid content and fatty acid composition in total lipid and lipid classes were determined in both rats. Seven pairs of rats from each group were treated in the same way. Calculations based on amount of linoleic acid ingested and retained in the carcass lipids showed that 50% of the ingested linoleic acid was retained in the low EFA rats compared to 10-15% in the normal and high EFA rats.

Topics: Animals; Body Weight; Dietary Fats; Fatty Acids; Fatty Acids, Essential; Female; Linoleic Acid; Linoleic Acids; Lipids; Male; Rats; Rats, Inbred Strains

Genetically obese mice (ob/ob) and their lean litter-mates were given diets iso-energetically supplemented with sucrose, hydrogenated coconut oil, safflower oil or evening primrose (Oenothera biennis) oil. Weight gain over 15 weeks was significantly greater in the evening primrose oil-supplemented obese mice than in the other groups. In all the groups of obese mice, liver total phospholipids contained proportionally less linoleic acid and more dihomo-gamma-linolenic acid and arachidonic acid than did the lean controls. As a percentage of total fatty acids, n-3 essential fatty acids (EFA) in liver and adipose tissue lipids were significantly lower in the obese mice than in the lean controls. Supplementation with EFA-rich oils (safflower and evening primrose oil) increased the proportional composition of n-6 EFA and decreased the n-3 EFA more in the liver total phospholipids of the lean than the obese mice.

Topics: Adipose Tissue; Animals; Body Weight; Epididymis; Fatty Acids, Essential; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids; Linolenic Acids; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Organ Size; Phospholipids; Triglycerides

Genetically diabetic mice (db/db) and their non-diabetic litter-mates were maintained for 15 weeks on diets supplemented with safflower oil or evening primrose (Oenothera bienis) oil, both essential fatty acid (EFA)-rich sources, or hydrogenated coconut oil (devoid of EFA). Plasma glucose was higher in the diabetic mice supplemented with the oils than in the unsupplemented diabetic mice. In the oil-supplemented non-diabetic mice, plasma glucose did not differ compared with the unsupplemented non-diabetic mice. The proportional content of arachidonic acid in the phospholipids of the pancreas was significantly decreased in diabetic mice, an effect which was completely prevented by supplementation with safflower or evening primrose oil but not hydrogenated coconut oil. In the liver phospholipids of the diabetic mice, dihomo-gamma-linolenic acid was proportionally increased, an effect reduced by supplementation with safflower oil but not evening primrose or hydrogenated coconut oils. In the liver triglycerides of the diabetic mice, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid were all proportionally decreased, effects which were also prevented by safflower or evening primrose oil but not hydrogenated coconut oil. Alopecia and dry scaly skin were prominent in the diabetic mice but less extensive in the diabetic mice supplemented with EFA.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Fatty Acids, Essential; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids; Linolenic Acids; Lipids; Liver; Mice; Mice, Inbred C57BL; Organ Size; Pancreas; Phospholipids; Skin; Triglycerides

High linoleic acid (C18:2) (group I; 17.7 cal%) and low C18:2 (group II; 3.3 cal%) diets were given to groups of inbred Brown Norway virgin female rats (100 animals/group), during their whole life-span. A total of 140 tumors were found in group I and 123 tumors in group II; the median survival times of the 2 groups were 124.2 and 118.5 weeks, respectively. Total spontaneous tumor incidence and median survival times were not significantly different. However, significant differences were found in the incidences of some specific tumors: The numbers of reticuloendothelial tumors and adrenocortical carcinomas were significantly higher in the group of animals receiving the low-C18:2 diet. A high incidence of tumor multiplicity, however, resulted in a significantly greater number of mammary tumors in the high-C18:2 diet group.

Topics: Adrenal Cortex Neoplasms; Age Factors; Animal Husbandry; Animals; Body Weight; Dietary Fats; Female; Linoleic Acid; Linoleic Acids; Mammary Neoplasms, Experimental; Neoplasms, Experimental; Pancreatic Neoplasms; Rats; Rats, Inbred BN

The influence of a supplement of linseed oil (LO), rich in linoleic acid (C18:3,n-3), was compared with one of fish oil (MaxEPA) rich in eicosapentaenoic acid (C20:5,n-3) and docosahexaenoic acid (22:6,n-3) on blood and tissue lipids in weanling rats receiving a high intake of linoleic acid. Both the LO and the MaxEPA supplement decreased plasma cholesterol concentrations. The MaxEPA supplement but not the linseed oil supplement also decreased the concentrations of plasma triglycerides and HDL cholesterol. The proportion of C20:5,n-3 was markedly increased in the platelet and erythrocyte lipids by the MaxEPA supplement but not in tissue lipids. However, the increase in the proportion of C20:5,n-3 in the platelet was small compared with other studies. Both supplements led to an increase in the proportion of C22:6,n-3 in blood and tissue lipids but the MaxEPA supplement was more potent than the LO supplement. The most marked change was observed in the heart lipids. These changes were accompanied by reciprocal changes in the proportions of arachidonic, adrenic and docosapentaenoic acid.

Topics: Adipose Tissue; Animals; Body Weight; Fatty Acids, Unsaturated; Linoleic Acid; Linoleic Acids; Lipids; Male; Myocardium; Rats; Rats, Inbred Strains

Rats from an inbred Sprague-Dawley strain were fed purified diets with a low (0.3% of the total energy), normal (3%) or high (10%) content of essential fatty acids (EFA) for several generations. Thirty- to 34-d-old male rats of at least the sixth generation to be fed these diets were given a single intragastric dose of [1-14C]linoleic acid in olive oil, and the respiratory CO2, urine and feces were collected for 20 h. The 14C activity was determined in the respiratory CO2, urine and feces as well as in total lipids and lipid classes of the whole animal and in nine tissue groups. The content of total lipids and lipid classes was similar in all groups. The rats in the low EFA group retained significantly more radioactivity (51%) in the tissues than the rats fed the normal EFA (34%) or the high EFA (27%) diets. In all groups most of the radioactivity was found in the skeletal muscles, skin, liver and white fat, but the retention was greater in the low EFA group than in the other groups, except in the white and brown fat. In the carcass and most tissues, the proportion of the retained 14C activity recovered in the phospholipids increased with decreasing EFA level in the diet, whereas in the triglycerides the opposite was found. Expressed as percent of administered dose, the total retention of radioactivity in the phospholipids was 31, 13 and 8% in the low, normal and high EFA group, respectively, while the retention in the triglycerides was about the same in all groups (17-18%).

Topics: Animals; Body Weight; Cholesterol Esters; Diet; Fatty Acids, Essential; Linoleic Acid; Linoleic Acids; Lipid Metabolism; Male; Organ Size; Phospholipids; Rats; Rats, Inbred Strains; Triglycerides

Two series of three consecutive 4-week experiments with a total of 1,370 Large White turkeys between 8 and 20 weeks of age were conducted to determine the effects of varying levels of dietary fat and protein on body weight gain and feed efficiency. Diets containing 0, 5, and 10% added fat and 18, 20, 22, and 24% protein in a 3 X 4 factorial were each fed to a total of three pens of males and three pens of females. At the end of each 4-week period, the turkeys were rerandomized to form 12 new equivalent groups, and similar diets with 2% less protein were fed. As part of this study, two fats, varying in fatty acid composition, were also compared but found not to affect significantly body weight gain or feed efficiency. Interaction effects of fat and protein on body weight gain, feed consumption, or feed efficiency were not significant. Body weight gain increased .5, .6, and 1.1%, feed consumption decreased 1.1, 1.0, and .9%, and feed efficiency increased 1.7, 1.8, and 2.2% for each 1% added fat during the 8 to 12-, 12 to 16-, and 16 to 20-week periods, respectively. The greater-than-expected increase in feed efficiency from added fat to diets of older turkeys is postulated to be due to stimulated feed consumption and body weight gain rather than to an extra caloric content of fat per se.

Topics: Aging; Animal Feed; Animals; Body Weight; Dietary Fats; Dietary Proteins; Eating; Energy Metabolism; Female; Linoleic Acid; Linoleic Acids; Male; Turkeys

To study the influence of dietary modification of prostaglandin synthesis on blood pressure regulation, the effects of dietary enrichment with linoleic acid were compared with standard rat chow in three groups of 24 rats before and after renal artery constriction and contralateral nephrectomy. Dietary supplementation with 40 energy% sunflower seed oil or linseed oil respectively caused incorporation of linoleic or linolenic acids into tissue phospholipids. Relative to the sunflower seed oil, the linseed oil diet led to inhibition of prostanoid synthesis in kidney, serum or aorta in vitro and urine in vivo. Rats on both oil-rich diets had lower blood pressures than rats on a standard diet. Thus, partial suppression of prostaglandin synthesis did not accelerate one-kidney, one clip Goldblatt hypertension, nor did sunflower oil protect against hypertension in a way that could be specifically ascribed to changes in prostaglandin synthesis.

Topics: 6-Ketoprostaglandin F1 alpha; alpha-Linolenic Acid; Animals; Aorta; Blood Pressure; Body Weight; Dietary Fats; Fatty Acids; Hypertension, Renovascular; Kidney; Linoleic Acid; Linoleic Acids; Linolenic Acids; Male; Prostaglandins; Rats; Thromboxanes

The lipid content as well as the fatty acid pattern of triglycerides, free fatty acids (FFA), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were estimated in renal cortex and medulla of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (WR) at 4, 8, 26 and 52 weeks of age. In general, the level of triglycerides in renal medulla appeared higher when compared with the cortex. On the other hand, PC and PE, increasing with age, were usually higher in the cortex. A decreased percentage of linoleic acid (LA) in triglycerides, of arachidonic acid (AA) in PC and of eicosapentaenoic acid (EPA) in triglycerides, FFA, PC and PE could be found in the kidneys of SHR at 8 weeks of age, i.e. during the development of hypertension. This was accompanied with a rise of AA in FFA of SHR at 8 weeks of age, which occurred with delay in WR (at 26 weeks of age). From the data presented it can be concluded that systematic alterations in the availability of individual polyunsaturated fatty acids (PUFA) in various renal lipids might be related to the onset of hypertension in SHR which should be elucidated in more detail.

Topics: Aging; Animals; Arachidonic Acid; Arachidonic Acids; Blood Pressure; Body Weight; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Unsaturated; Hypertension; Kidney Cortex; Kidney Medulla; Linoleic Acid; Linoleic Acids; Phospholipids; Rats; Rats, Mutant Strains; Triglycerides

The effects of dietary unsaturated and saturated fats on chemically induced colon carcinogenesis were examined in male Donryu rats. The rats were fed two types of semipurified diets consisting of 5% linoleic acid or 4.7% stearic acid plus 0.3% essential fatty acid as dietary fats. The rats were treated with azoxymethane (7.4 mg/kg body weight) s.c. once a week for 11 weeks and sacrificed 15 weeks after the last injection of the carcinogen. The rats fed unsaturated fat diet demonstrated a significantly higher incidence of colon tumors [100%], more tumors per rat [2.68 +/- 1.60 (S.D.)], and greater malignant differentiation histologically than did those fed saturated fat diet [76%, 1.79 +/- 1.59, respectively]. Lipid analysis of colon tumors and colon mucosa showed that unsaturated fat diet altered the phosphatide fatty acyl composition of colon mucosa markedly and increased the content of arachidonic acid in the neutral lipid of colon tumors. The altered lipid composition of the mucosa may increase the sensitivity of the colon to the carcinogen, and the excess of arachidonic acid or its metabolites may be the primary agents of cocarcinogenesis of colon tumors. These findings suggest that dietary unsaturated fats have potent cocarcinogenic effects on colon carcinogenesis.

Topics: Animals; Azoxymethane; Body Weight; Colon; Colonic Neoplasms; Dietary Fats; Fatty Acids; Intestinal Mucosa; Linoleic Acid; Linoleic Acids; Liver; Male; Phospholipids; Rats; Rats, Inbred Strains; Stearic Acids

The effects of dietary linoleic acid on the serum level of high density lipoprotein (HDL) cholesterol and its relationship with the tissue status of zinc and copper were examined in adult male rats fed diets differing in the amount of linoleic acid. One group of 9 animals was fed a diet containing hydrogenated coconut oil (4%) and the other was fed a diet containing coconut oil (3.4%) plus linoleic acid (0.6%). Both diets were isocalorically formulated with the equal levels of minerals and other nutrients and contained cholesterol at 1% level. During a 6-week experiment, no differences were observed in food intake and body weight between the two groups. The feeding of linoleic acid produced a significant decrease in serum HDL cholesterol level at 6 weeks and no changes in other lipoproteins and total serum cholesterol and triglyceride. Dietary linoleic acid also significantly lowered the concentrations of zinc in serum and tibia at 6 weeks, while it had no effect on copper contents in these tissues. No changes were observed in the concentration of either zinc or copper in the liver. Linear regression analysis of the 18 pairs of serum zinc and HDL values at 6 weeks indicated a significant positive correlation (r = +0.65; P less than 0.01) between the two parameters. No such relationships were shown between tibia zinc and serum HDL, and between tissue copper and serum HDL. The results indicate that dietary linoleic acid at a relatively low level produces a decrease in serum HDL cholesterol without significantly lowering total serum cholesterol and that the decrease in HDL cholesterol due to linoleic acid feeding is significantly correlated with the reduction in serum zinc level.

Topics: Animals; Body Weight; Cholesterol; Cholesterol, HDL; Copper; Dietary Fats; Linoleic Acid; Linoleic Acids; Lipoproteins, HDL; Male; Rats; Rats, Inbred F344; Zinc

A factorial experiment involving gnotobiotic (GN) and conventional (CV) colostrum-deprived lambs and diets formulated to be adequate or deficient in linoleic acid was conducted to determine the effect(s) of the intestinal microflora on the essential fatty acid (EFA) status of the host and subsequent physiological consequences, i.e., growth, organ development, cell membrane integrity and lower bowel function. Lambs were obtained by sterile surgical procedures and housed in sterile isolators or in conventional metabolism stalls for 60 d. Skimmed cow's milk with 6% hydrogenated coconut oil and vitamins A, D and E added with and without .32% of the total calories as linoleic acid was homogenized, bottled and autoclaved, then fed to appetite three to four times daily. The GN lambs supplemented with linoleic acid gained significantly faster between 13 and 41 d of age and more efficiently between 27 and 41 d than the other treatment groups. The absence of dietary linoleic acid decreased liver and spleen weights and, in general, suppressed development of organs except the brain. Red blood cell hemolysis was not affected by treatment. Although showing signs of chronic mild diarrhea, the GN neonatal ruminant differed in Cl- concentration and dry matter percentage of its lower bowel contents from the "classic rodent model." The results indicate that neonatal colostrum-deprived lambs have an EFA requirement, as evidenced by decreased growth and performance characteristics in the GN linoleic deficient vs GN supplemented group, and suggests that the required level is in excess of .32% of the total caloric intake as linoleic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Cell Membrane Permeability; Colostrum; Dietary Fats; Fatty Acids, Essential; Germ-Free Life; Intestines; Linoleic Acid; Linoleic Acids; Organ Size; Sheep

The interrelationships of dietary vitamin E and essential fatty acids and their effects on serum and pulmonary prostaglandin (PG) synthesis and fatty acid precursors were examined. In a preexperimental period, male weanling rats were depleted of essential fatty acids (EFA) by feeding on a hydrogenated coconut oil diet. At the end of 45 days, average serum triene:tetraene ratio for the EFA-deficient rats was 0.76. After a refeeding period with a 20% safflower oil diet and 0, 1 or 50 mg of dl-alpha-tocopheryl acetate daily, serum and pulmonary fatty acid profiles and PG synthesis were determined. A trend to growth depression on the high vitamin E diet was observed. Vitamin E supplementation seemed to have no significant effect on fatty acid composition or synthesis of PGE1, PGE2, PGF2 alpha or PGI2 in lung. This may be due to the small lipid content and presumed inability of lung to accumulate excess vitamin E. Lung may, therefore, be resistant to such dietary manipulations. Serum PG synthesis was not affected by vitamin E dose, although the C20:4 omega 6/C18:2 omega 6 ratio in serum was significantly lowered on the high vitamin E diet.

Topics: Animals; Body Weight; Diet; Dietary Fats; Dose-Response Relationship, Drug; Fatty Acids; Linoleic Acid; Linoleic Acids; Lung; Male; Prostaglandins; Rats; Rats, Inbred Strains; Vitamin E

Sunflower and olive oils were fed at the same dietary inclusion levels to male broilers as a means of varying the dietary linoleic acid concentration while maintaining similar concentrations of total fat and total unsaturated fatty acids. The type of oil and the dietary supplementation level influenced growth rate, food utilisation and carcass composition. Birds grew faster and utilised food more efficiently when fed the sunflower oil and had higher concentrations of body fat. Increasing the level of supplementation with either oil decreased body fat content. The different responses to the two oils were not related to differences in dietary amino acid balance, ME: protein ratios or rates of food passage through the digestive tract.

Topics: Animals; Body Composition; Body Weight; Chickens; Dietary Fats; Food, Fortified; Linoleic Acid; Linoleic Acids; Lipids; Male; Oils; Plant Oils; Proteins; Sunflower Oil

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Dietary Fats; Energy Intake; Fatty Acids; Half-Life; Linoleic Acid; Linoleic Acids; Male; Mice; Mice, Inbred Strains

The effect of dietary variations in linoleic acid (LA) on the development of hypertension was studied in young male spontaneously hypertensive rats (SHR). All groups developed elevated systolic blood pressures, but after 7 weeks on the experimental diets the blood pressures of the rats fed the diet with a low LA content (0.17% as supplied by 8% coconut oil) were significantly lower than the group fed a high level of LA (9.5% as supplied by 17% corn oil) in the diet. Rats fed the high LA diet had increased urine output and developed a mild but persistent polydipsia. After 4 months on the experimental diets, potassium excretion was decreased in proportion to the amount of LA in the diet but sodium excretion was not altered. Serum potassium was significantly elevated in the group fed high LA after 5 months. The effects of LA on hypertension of SHR appear to be opposite to those observed during salt-induced hypertension. Since LA is the dietary precursor of the prostaglandins, the effects observed may be due to the availability of precursor for renal prostaglandin synthesis which has been reported to be altered in SHR.

Topics: Animals; Blood Pressure; Body Weight; Dietary Fats; Dose-Response Relationship, Drug; Drinking; Hypertension; Linoleic Acid; Linoleic Acids; Male; Potassium; Rats; Sodium; Urine

Topics: Adipose Tissue; Body Weight; Cholesterol; Coronary Disease; Diet; Diet Therapy; Dietary Fats; Fats, Unsaturated; Fatty Acids; Histocytochemistry; Humans; Linoleic Acid; Lipid Metabolism; Male

Topics: Arachis; Body Weight; Butter; Cocos; Dietary Fats; Feces; Intestines; Linoleic Acid; Metabolism; Pharmacology; Rats; Research; Sesame Oil; Thiamine; Thiamine Deficiency; Urine

Topics: Animals; Aorta; Arteriosclerosis; Body Weight; Butter; Cholesterol; Coronary Vessels; Diet; Dietary Fats; Hypercholesterolemia; Kidney; Linoleic Acid; Liver; Metabolism; Myocardium; Oils; Oils, Volatile; Pathology; Rabbits; Research; Starch

Topics: Blood Chemical Analysis; Body Weight; Calcium; Calcium, Dietary; Dietary Fats; Fats, Unsaturated; Fatty Acids; Fatty Acids, Essential; Glycerides; Kidney Calculi; Linoleic Acid; Palmitic Acid; Rats; Research; Toxicology; Vitamin D

Topics: Animals; Arteriosclerosis; Atherosclerosis; Blood Chemical Analysis; Body Weight; Cholesterol; Dietary Proteins; Fatty Acids; Fatty Acids, Essential; Heparin; Hexosamines; Hypertension; Hypertension, Renal; Lanolin; Linoleic Acid; Lipoproteins; Pathology; Phospholipids; Rabbits; Research; Urea

Topics: Animals; Blood Chemical Analysis; Body Weight; Carbohydrate Metabolism; Chemical Phenomena; Chemistry; Chickens; Cholesterol; Diet; Dietary Proteins; Fatty Acids; Glycerides; Linoleic Acid; Lipid Metabolism; Lipidoses; Lipids; Liver; Oleic Acid; Phospholipids; Poultry; Research

Topics: Animals; Body Weight; Body Weights and Measures; Fatty Acids; Linoleic Acid; Rats; Saponins; Sterols; Weight Gain