linoleic-acid and Hyperlipidemias

Peroxisome proliferator-activated receptor α (PPARα) is one of the three isoforms of PPARs, which are ligand-activated nuclear transcription factors. PPARα is highly expressed in liver and its agonists are widely used to treat hyperlipidemia. Epidermal keratinocytes express all three isoforms (α, β/δ, and γ) of PPARs and PPARα is particularly important for regulating the epidermal barrier and inflammation. Agonistic ligation of PPARα protects the epidermal barrier function and inhibits the inflammatory response in dermatitis. In this review, we summarize recent topics on the role of PPARα in skin biology and discuss the potential use of topical PPARα agonists for treating atopic dermatitis and other eczemas.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Dermatitis; Fenofibrate; Filaggrin Proteins; Humans; Hyperlipidemias; Keratinocytes; Linoleic Acid; Liver; PPAR alpha; Skin

Topics: Adipose Tissue; Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Animals; Clinical Trials as Topic; Colforsin; Energy Metabolism; Humans; Hyperlipidemias; Linoleic Acid; Lipid Metabolism; Thermogenesis

Topics: Adult; Arteriosclerosis; Cholesterol, Dietary; Coronary Disease; Diet, Atherogenic; Diet, Vegetarian; Dietary Carbohydrates; Dietary Fats; Eicosanoids; Energy Intake; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Feeding Behavior; Female; Humans; Hyperlipidemias; Incidence; Linoleic Acid; Linoleic Acids; Lipids; Lipoproteins; Male; Middle Aged; Molecular Structure; Obesity; Prevalence; Risk Factors

Children affected by primary hyperlipidemia have a high risk of developing cardiovascular diseases (CVDs) during adulthood. Several studies have reported a positive association between the intake of polyunsaturated fatty acids (PUFAs) and improvements in lipid markers and CVD risk. Dietary supplements may represent a potential strategy in the management of hyperlipidemia. In this context, the effectiveness of hempseed oil (HSO) rich in PUFAs (particularly linoleic acid (LA) and α-linolenic acid (ALA)) in the modulation of hyperlipidemia has been poorly investigated. The present pilot study aimed to explore the impact of HSO supplementation on the serum lipid profile and fatty acid (FA) composition of red blood cells (RBCs) in children and adolescents with primary hyperlipidemia. A randomized, 8 week long, parallel dietary intervention study was performed. Thirty-six hyperlipidemic probands (6-16 years) on diet therapy were randomized into two groups: the HSO group, receiving 3 g of HSO providing 1.4 g of LA and 0.7 g/day of ALA, and the control group. Both groups received specific dietary guidelines. Before and after the intervention, blood samples were collected and the serum lipid profile, FA composition of RBCs and omega-3-index were analyzed. Eight weeks of supplementation with HSO significantly (p < .01) reduced the RBC content of total saturated and monounsaturated FAs (-5.02 ± 7.94% and - 2.12 ± 2.23%, respectively), increased the levels of total n-3 and n-6 PUFAs (+1.57 ± 1.96% and + 5.39 ± 7.18%, respectively) and the omega-3 index (+1.18 ± 1.42%), but failed to affect the serum lipid profile compared to the control group. In conclusion, our findings seem to support the contribution of HSO supplementation in improving the RBC phospholipid composition and omega-3 index, while no effect was observed regarding modulation of the lipid profile. Further controlled studies are necessary to achieve a complete understanding of the effects of HSO in the modulation of hyperlipidemia and CVD risk in this and other target groups.

Topics: Adolescent; alpha-Linolenic Acid; Child; Dietary Supplements; Erythrocytes; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Humans; Hyperlipidemias; Linoleic Acid; Male; Phospholipids; Pilot Projects

Conjugated linoleic acid (CLA) is a group of dietary fatty acids with antiobesity and antidiabetic effects in some animals. The trans10cis12 (t10c12) CLA isomer seems to cause these effects, including improved insulin sensitivity. Whether such isomer-specific effects occur in humans is unknown. The aim of this study was to investigate whether t10c12 CLA or a commercial CLA mixture could improve insulin sensitivity, lipid metabolism, or body composition in obese men with signs of the metabolic syndrome.. In a randomized, double-blind controlled trial, abdominally obese men (n = 60) were treated with 3.4 g/day CLA (isomer mixture), purified t10c12 CLA, or placebo. Euglycemic-hyperinsulinemic clamp, serum hormones, lipids, and anthropometry were assessed before and after 12 weeks of treatment.. Baseline metabolic status was similar between groups. Unexpectedly, t10c12 CLA increased insulin resistance (19%; P < 0.01) and glycemia (4%; P < 0.001) and reduced HDL cholesterol (-4%; P < 0.01) compared with placebo, whereas body fat, sagittal abdominal diameter, and weight decreased versus baseline, but the difference was not significantly different from placebo. The CLA mixture did not change glucose metabolism, body composition, or weight compared with placebo but lowered HDL cholesterol (-2%; P < 0.05).. These results reveal important isomer-specific metabolic actions of CLA in abdominally obese humans. A CLA-induced insulin resistance has previously been described only in lipodystrophic mice. Considering the use of CLA-supplements among obese individuals, it is important to clarify the clinical consequences of these results, but they also provide physiological insights into the role of specific dietary fatty acids as modulators of insulin resistance in humans.

Topics: Adult; Aged; Body Composition; Diabetes Mellitus; Double-Blind Method; Humans; Hyperlipidemias; Insulin Resistance; Isomerism; Leptin; Linoleic Acid; Lipoproteins; Male; Metabolic Syndrome; Middle Aged; Obesity

To compare two low fat diets one rich in walnuts on parameters of lipid metabolism in a group of hyperlipidaemic subjects.. A randomised cross over study.. Department of Human Nutrition, University of Otago, Dunedin, New Zealand. Twenty one men with mean (s.d.) levels of total and LDL cholesterol of 6.58 (0.60) and 4.63 (0.58) respectively.. For two periods of four weeks subjects were asked to consume two low fat diets (fat 30% total energy), one containing, on average, 78 g/d walnuts. Walnuts obtained through Lincoln University and the Walnut Growers Group (South Canterbury).. Participants reported a higher total fat intake on the walnut diet (38% compared with 30% on the low fat diet P < 0.01) The most consistent change in fatty acid profile of triacylglycerol, phospholipid and cholesterol ester on the walnut diet was a significant (P < 0.01) increase in linoleic acid. Triacylglycerol linolenate also increased significantly (P < 0.01). Total and LDL cholesterol were lower on both experimental diets than at baseline, 0.25 mmol/l and 0.36 mmol/l respectively on the walnut diet and 0.13 mmol/l and 0.20 mmol/l respectively on the low fat diet. High density lipoprotein cholesterol was higher on both the walnut and low fat diets when compared to baseline (0.15 mmol/l and 0.12 mmol/l, respectively). When comparing the walnut and low fat diets only apo B was significantly lower (P < 0.05) on the walnut diet.. Despite an unintended increase in the total fat intake on the walnut diet, fatty acid profile of the major lipid fractions showed changes which might be expected to reduce risk of cardiovascular disease. The reduction of apolipoprotein B suggests a reduction in lipoprotein mediated risk, the relatively low myristic acid content of both diets perhaps explaining the absence of more extensive differences in lipoprotein levels on the two diets.

Topics: Adult; alpha-Linolenic Acid; Cholesterol; Cholesterol Esters; Cholesterol, LDL; Cross-Over Studies; Diet; Dietary Fats; Fatty Acids; Humans; Hyperlipidemias; Linoleic Acid; Male; Middle Aged; Nuts; Phospholipids; Triglycerides

The long-term effects of practical amounts of fish oil on plasma lipids and lipoprotein cholesterol levels, bleeding times, erythrocyte deformabilities, and plasma phospholipid fatty acid (FA) composition were investigated in this trial. Twenty-eight hyperlipidemic patients with elevated cholesterol and triglyceride (TG) levels were randomly assigned to take 3, 6, 9, or 12 capsules of fish oil daily for 6 months, providing 1.25-5 g of n-3 FAs per day. Baseline parameters were compared to values after 1 and 6 months of treatment, and after 1 month of washout. There were no statistically significant changes in total cholesterol levels at any dose. Both low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels tended to rise, resulting in an unchanged ratio of LDL-C to HDL-C. The TG and very-low-density-lipoprotein cholesterol (VLDL-C) levels decreased significantly with all but the lowest dose. Bleeding times were unaffected despite a nonsignificant 34% increase detected at the highest dose. Red blood cell deformability tended to increase with the two middle doses only. The EPA level in plasma phospholipids was strongly correlated with n-3 FA (FA) consumption. We conclude that long-term treatment of hyperlipidemic patients with practical intakes of n-3 FAs produced persistent reductions in TG levels and no change in the LDL-C/HDL-C ratio.

Topics: Arachidonic Acid; Arachidonic Acids; Bleeding Time; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diet Records; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocyte Deformability; Fatty Acids, Omega-3; Humans; Hyperlipidemias; Linoleic Acid; Linoleic Acids; Random Allocation; Triglycerides

After diets supplemented with canned mackerel or herring, in a cross-over design, containing different amounts of long-chain n-3 fatty acids (eicosapentaenoic acid, C20:5n-3-EPA, and docosahexaenoic acid, C22(6)n-3-DHA) an increase of both EPA and DHA was confirmed in triglycerides (TG), cholesterol esters (CE) and phospholipids (PL) of very low density (VLDL) and low density lipoproteins (LDL) as well as in high density lipoproteins (HDL) from hyperlipidemic subjects. An unexpected finding was the simultaneous increase of arachidonic acid (C20:4n-6-AA) in TG and CE and its constant portion in PL of lipoproteins, whereas linoleic acid (C18:2n-6-LA) appeared lower in CE and in PL of VLDL + LDL and HDL. In general, the changes were minor after a diet supplemented with canned herring providing a lower dose of n-3 fatty acids. The results indicate dose-related changes not only of n-3 fatty acids, but also of n-6 fatty acids in serum lipids after fish diets. This different behavior of LA and AA in serum lipids might be a new aspect in the interrelations and the dietary modulation of both families of polyunsaturated fatty acids (PUFA). The accumulation of AA in neutral lipids could be linked with an elevation of prostaglandin I2, which was found apart from an increased formation of prostaglandin I3 after diets supplemented with n-3 fatty acids. The concomitant increase of prostaglandins I2 and I3 spotlights widely ignored interrelations within the eicosanoid pathway, which become evident after diets enriched with long-chain n-3 fatty acids.

Topics: Adult; Arachidonic Acid; Arachidonic Acids; Blood Pressure; Dietary Fats, Unsaturated; Fatty Acids, Unsaturated; Female; Fish Oils; Humans; Hyperlipidemias; Linoleic Acid; Linoleic Acids; Lipids; Lipoproteins; Male; Middle Aged

Effects of a daily fish-oil supplement on serum lipids, apolipoproteins, and some platelet functions and hemorheologic variables were examined in 27 hyperlipidemic subjects in a randomized, controlled, double-blind, crossover fashion with an identically encapsulated vegetable oil serving as the control treatment. Despite the habitual high linoleic acid intake of the study population, significant incorporation of n-3 (omega-3) fatty acids into the serum, platelet, and erythrocyte lipids was observed after the fish-oil supplement. Ingestion of fish oil resulted in a 40% decrease in the triglyceride concentration, a 12% increase in HDL cholesterol, and a significant decrease in plasma viscosity, whereas the vegetable-oil placebo had no significant effect. We conclude that a moderate intake of fish oil (15 g/d) is a feasible treatment for hypertriglyceridemia even in patients with a background of high linoleic acid intake and that it may have a beneficial effect on several cardiovascular risk factors.

Topics: Apolipoproteins; Blood Platelets; Blood Viscosity; Cardiovascular Diseases; Cholesterol; Double-Blind Method; Erythrocyte Deformability; Fatty Acids; Fish Oils; Humans; Hyperlipidemias; Israel; Linoleic Acid; Linoleic Acids; Lipids; Platelet Aggregation; Risk Factors; Triglycerides

In normal, hypertensive and hyperlipemic subjects, diets supplemented with linoleic acid (LA) or alpha-linolenic acid (LNA) resulted in an increase of the corresponding fatty acids in serum lipids. However, their C20-derivatives, the prostaglandin precursors arachidonic acid (AA) and eicosapentaenoic acid (EPA), respectively, were not or only slightly augmented. On the other hand, an EPA-rich diet produced a marked increase of this fatty acid, especially in cholesterol esters. After this diet the decreases of blood pressure and serum lipids were more pronounced when compared with LA- and LNA-rich diets containing a 20-fold higher dose of the polyunsaturated fatty acids. The slow formation of AA and EPA from LA and LNA seems to be a characteristic finding in humans, being different from preferred laboratory animals, for instance, rats. This observation was independent of the presence of risk factors, like arterial hypertension or hyperlipoproteinemia (HLP).

Topics: Adult; alpha-Linolenic Acid; Arachidonic Acid; Arachidonic Acids; Blood Pressure; Dietary Fats; Eicosapentaenoic Acid; Fatty Acids; Humans; Hyperlipidemias; Hypertension; Linoleic Acid; Linoleic Acids; Linolenic Acids; Lipids; Lipoproteins; Male; Middle Aged

Tartary buckwheat can improve hyperlipidemia and affect the changes of metabolic pathways to the body. In this study, we use LC/MS to obtain metabolic fingerprints of plasma samples collected from control (LFD), high-fat diet (HFD), Tartary buckwheat protein (BWP), and Tartary buckwheat starch (BWS). Using the metabolic network database, through OPLS-DA, the potential biomarkers and pathways of BWP and BWS intervention in hyperlipidemia mice are initially determined. The results showed that there are 30 metabolites in total, among which linoleic acid, glycerol, phosphatidyl, ethanolamine, and galactose ceramide are the most important differentially expressed metabolites in BWP and BWS plasma samples. These metabolites are involved in eight metabolic pathways, such as linoleic acid metabolism, arachidonic acid metabolism. Tartary buckwheat can alleviate the symptoms of hyperlipidemia in mice by affecting the above-mentioned metabolic pathways. This research has a profound impact on the development of nutritious foods of buckwheat. PRACTICAL APPLICATIONS: Tartary buckwheat, also known as wild buckwheat, is a typical embodiment homology of medicine and food. We have clarified that the protein and starch extracted from tartary buckwheat have the function of reducing blood lipids. It is expected to be applied to functional food materials in the health food market. Also, the effects of tartary buckwheat protein and starch in improving metabolic pathways can be generally applied as a physiological active compound of functional food supplements.

Topics: Animals; Arachidonic Acid; Ceramides; Ethanolamines; Fagopyrum; Galactose; Hyperlipidemias; Linoleic Acid; Metabolomics; Mice; Phosphatidylglycerols; Starch

Both hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics.. This was a case‒control study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software.. The prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway.. Compared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.

Topics: Alanine; Aspartic Acid; Biomarkers; Case-Control Studies; Glycine; Humans; Hyperlipidemias; Hyperuricemia; Linoleic Acid; Mass Spectrometry; Metabolic Diseases; Metabolic Networks and Pathways; Phenylalanine; Serine; Threonine; Tryptophan; Tyrosine

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

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

To investigate the metabolite changes caused by simvastatin or fenofibrate intervention in diet-induced hyperlipidemia rats using a GC-MS-based metabolomic profiling approach.. SD rats were fed with high-lipid diet for 4 weeks to induce hyperlipidemia, then the rats were fed with normal diet, and orally administered with simvastatin (10 mg·kg(-1)·d(-1)) or fenofibrate (150 mg·kg(-1)·d(-1)) for 2 weeks. Blood samples were collected once a week, and potential biomarkers were examined using commercial assay kits and a metabolomic approach. The metabolomics data were analyzed using a multivariate statistical technique and a principal component analysis (PCA).. Oral administration of simvastatin or fenofibrate significantly decreased the plasma levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol and increased the plasma level of high-density lipoprotein (HDL) cholesterol in the hyperlipidemia rats. Plasma samples were scattered in the PCA scores plots in response to the diet and to the drugs administered. The main metabolites changed in the hyperlipidemia rats were cholesterol, creatinine, linoleic acid, β-hydroxybutyric acid, tyrosine, isoleucine and ornithine. The plasma level of creatinine was significantly lower in the simvastatin-treated rats than in the fenofibrate-treated rats. The plasma tyrosine concentration was declined following intake of high-lipid diet, which was reversed by fenobrate, but not by simvastatin.. A series of potential biomarkers including tyrosine, creatinine, linoleic acid, β-hydroxybutyric acid and ornithine have been identified by metabolomic profiling, which may be used to identify the metabolic changes during hyperlipidemia progression.

Topics: 3-Hydroxybutyric Acid; Animals; Biomarkers; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Creatinine; Diet, High-Fat; Fenofibrate; Hyperlipidemias; Isoleucine; Linoleic Acid; Male; Metabolome; Metabolomics; Ornithine; Rats; Rats, Sprague-Dawley; Simvastatin; Tyrosine

Cornus wilsoniana Wanger is a woody oil plant distributed in the south region of the Yellow River, China. Its oil has been taken as edible oil for over 100 y, and consumption of such oil is believed to prevent hyperlipidemia in Chinese folk recipe. This study has investigated the hypolipidemic effect of Cornus wilsoniana oil (CWO) in Sprague-Dawley rats. The results demonstrated that CWO could significantly decrease total cholesterol (TC), total triacylglycerol (TG), and low-density lipoprotein cholesterol (HDL-C) in serum, liver weight, hepatic TC, and TG. After analyzing the chemical constituents of CWO, we found that the content of unsaturated fatty acids (UFA) was very high (69.12%). Specially, the n-6 polyunsaturated fatty acids (PUFA), including linoleic acid, γ-linolenic acid, and 11,14-eicosadienoic acid, accounted very great proportion (38.86%). The high hypolipidemic activity of CWO might be attributed to the lipid-lowering functions of these polyunsaturated fatty acids. Molecular docking was further performed to study the binding model of fatty acids (FA) from CWO to a possible hypolipidemic target, peroxisome proliferator-activated receptor δ (PPARδ). The results showed that linoleic acid and γ-linolenic acid could bind PPARδ very well.. Cornus wilsoniana oil could be used as equilibrated dietary oil, not only having hypolipidemic function, but also helping to overcome essential fatty acids deficiency.

Topics: Animals; China; Cholesterol, LDL; Cornus; Dietary Fats, Unsaturated; Eicosanoic Acids; Fruit; gamma-Linolenic Acid; Hyperlipidemias; Hypolipidemic Agents; Linoleic Acid; Liver; Male; Plant Oils; PPAR delta; Rats; Rats, Sprague-Dawley; 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

Topics: Adult; Aged; Animals; Atherosclerosis; Cholesterol, LDL; Coronary Disease; Denmark; Dietary Fats; Eicosanoids; Endothelium, Vascular; Energy Metabolism; Fatty Acids; Fatty Acids, Nonesterified; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Fish Oils; Gene Expression Regulation; Greenland; Health Surveys; Humans; Hyperlipidemias; Inflammation; Linoleic Acid; Male; Middle Aged; Nurses; Triglycerides; United States

Topics: Fatty Acids; Gemfibrozil; Humans; Hyperlipidemias; Hypolipidemic Agents; Linoleic Acid; Lipids; Oleic Acid; Palmitic Acid; Serum; Stearic Acids

Maillard or browning reactions between reducing sugars and protein lead to formation of advanced glycation end products (AGEs) and are thought to contribute to the pathogenesis of diabetic complications. AGE inhibitors such as aminoguanidine and pyridoxamine (PM) inhibit both the formation of AGEs and development of complications in animal models of diabetes. PM also inhibits the chemical modification of protein by advanced lipoxidation end products (ALEs) during lipid peroxidation reactions in vitro. We show here that several PM adducts, formed in incubations of PM with linoleate and arachidonate in vitro, are also excreted in the urine of PM-treated animals. The PM adducts N-nonanedioyl-PM (derived from linoleate), N-pentanedioyl-PM, N-pyrrolo-PM, and N-(2-formyl)-pyrrolo-PM (derived from arachidonate), and N-formyl-PM and N-hexanoyl-PM (derived from both fatty acids) were quantified by liquid chromatography-mass spectrometry analysis of rat urine. Levels of these adducts were increased 5-10-fold in the urine of PM-treated diabetic and hyperlipidemic rats, compared with control animals. We conclude that the PM functions, at least in part, by trapping intermediates in AGE/ALE formation and propose a mechanism for PM inhibition of AGE/ALE formation involving cleavage of alpha-dicarbonyl intermediates in glycoxidation and lipoxidation reactions. We also conclude that ALEs derived from polyunsaturated fatty acids are increased in diabetes and hyperlipidemia and may contribute to development of long term renal and vascular pathology in these diseases.

Topics: Animals; Arachidonic Acid; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Fatty Acids, Unsaturated; Female; Hyperlipidemias; Linoleic Acid; Lipid Peroxidation; Pyridoxamine; Rats; Rats, Sprague-Dawley; Rats, Zucker; Triglycerides

Blood samples were collected from 26 captive-reared alligators (25 females; one male) and 12 (seven females and five males) wild "nuisance" alligators collected by wildlife personnel in south Louisiana in May 1995. The captive alligators, hatched from artificially incubated eggs in 1972-1973, had received vitamin E supplements during the 3 weeks before the blood sample was collected. Each sample was analyzed for vitamin E (alpha-tocopherol), vitamin A (retinol), total lipid, triacylglycerol, phospholipid, cholesterol, cholesteryl ester, free fatty acids, steroid hormones and a standard clinical blood panel. The fatty acid composition of the plasma lipid fraction was also analyzed. Results indicated that 18 of the captive females and three of the seven wild females were undergoing vitellogenesis, i.e. had elevated plasma estradiol and elevated plasma calcium. Vitellogenic females had higher vitamin E than non-vitellogenic females (77.4 microg/ml vs. 28.6 microg/ml in captive females; 24.0 microg/ml vs. 21 microg/ml in wild females). Plasma retinol was similar in all groups, ranging from 0.5 to 1.4 microg/ml and close to values reported in birds. All lipid fractions, with the exception of cholesteryl ester, were higher in captive alligators than in wild alligators. There were also significant differences in the fatty acid composition of wild and captive alligators. Plasma eicosapentaenoic and docasahexaenoic acid were higher in wild than in captive alligators, whereas linoleic was higher in captive than in wild.

Topics: Alligators and Crocodiles; Animals; Calcium; Chromatography, High Pressure Liquid; Docosahexaenoic Acids; Eicosapentaenoic Acid; Estradiol; Fatty Acids; Female; Hyperlipidemias; Infertility; Linoleic Acid; Lipids; Male; Steroids; Time Factors; Vitamin A; Vitamin E

Insulin resistance and type 2 diabetes are associated with elevated circulating levels of insulin, nonesterified fatty acids (NEFAs), and lipoprotein remnants. Extracellular matrix proteoglycan (PG) alterations are also common in macro- and microvascular complications of type 2 diabetes. In liver, extracellular heparan sulfate (HS) PGs contribute to the uptake of triglyceride-rich lipoprotein remnants. We found that HepG2 cells cultured with 10 or 50 nmol/l insulin or 300 micromol/l albumin-bound linoleic acid changed their PG secretion. The glycosaminoglycans (GAGs) of the secreted PGs from insulin-treated HepG2 cells were enriched in chondroitin sulfate (CS) PGs. In contrast, cells exposed to linoleic acid secreted PGs with decreased content of CS. Insulin caused a moderate increase in mRNA for versican (secreted CS PG), whereas linoleic acid markedly decreased mRNA for versican in HepG2 cells, as did the peroxisomal proliferator-activated receptor-alpha agonist bezafibrate. The effects of insulin or linoleic acid on syndecan 1, a cell surface HS PG, were similar to those on versican, but less pronounced. The livers of obese Zucker fa/fa rats, which are insulin-resistant and have high levels of insulin, NEFAs, and triglyceride-rich remnants, showed increased expression of CS PGs when compared with lean littermates. These changes in PG composition decreased the affinity of remnant beta-VLDL particles to PGs isolated from insulin-treated HepG2 cells and obese rat livers. The results indicated that insulin and NEFAs modulate the expression of PGs in hepatic cells. We speculate that in vivo this exchange of CS for HS may reduce the clearance of remnant beta-VLDLs and contribute to the dyslipidemia of insulin resistance.

Topics: Animals; Cell Line; Extracellular Matrix; Fatty Acids; Humans; Hyperlipidemias; Insulin; Insulin Resistance; Linoleic Acid; Lipoproteins, VLDL; Liver; Obesity; Proteoglycans; Rats; Rats, Zucker; Thinness

Previous studies indicate a particular sensitivity of red blood cell Na(+)-Li+ countertransport activity to small variations in the fatty acid composition of membrane phospholipids. To assess whether the interindividual variability of Na(+)-Li+ countertransport is related to differences in the species pattern of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in vivo, the molecular species composition of PC and PE as well as the kinetics of Na(+)-Li+ countertransport were analyzed in parallel in normo- and hyperlipidemic donors. Both in diacyl-PC and in diacyl-PE the species 16:0/20:4 and 16:0/18:2 were, respectively, positively and negatively related to the apparent maximal velocity of Na(+)-Li+ countertransport. The sum of all species with 20:4 at sn2 of diacyl-PE exhibited a strong positive (r = 0.82, 2p < 0.001), and those containing 18:2 a negative correlation (r = -0.63, 2p < 0.01) to the transport activity. Essentially similar connections were observed between these species and the apparent affinity of the transport system for intracellular Na+. To evaluate whether the associations between molecular species of membrane phospholipids and Na(+)-Li+ countertransport activity were indicative of a causal relationship, the species 16:0/20:4-PC and 16:0/18:2-PC were selectively introduced into the erythrocyte membrane by means of the PC-specific transfer protein. Replacement of 11% of native PC by 16:0/18:2-PC inhibited the transport rate by about 25%. Exchange of 6 and 9% of PC with 16:0/20:4-PC, in contrast, accelerated the transport rate by 30 and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arachidonic Acid; Erythrocyte Membrane; Humans; Hyperlipidemias; In Vitro Techniques; Ion Transport; Kinetics; Linoleic Acid; Linoleic Acids; Lithium; Membrane Lipids; Phosphatidylcholines; Phosphatidylethanolamines; Sodium

Tumor growth and the incorporation of [3H]thymidine into tumor DNA in vivo are increased about 3 times in adult rats (greater than 250 g) after 1 to 2 days of starvation or the induction of diabetes with streptozotocin. These tumor growth responses require hyperlipemia and are reversed by refeeding or insulin treatment, respectively. They do not occur in young tumor-bearing rats (less than about 150 g) that lack appreciable fat stores. A direct relationship between the increased rates of both [3H]thymidine incorporation and tumor growth and host hyperlipemia suggests that tumor cell renewal in vivo in fed rats is limited by substances that are present in hyperlipemic blood. In this study we used a procedure for perfusion of solid tumors in situ to measure the sensitivity of tumor [3H]thymidine incorporation to hyperlipemic blood and to identify the rate-limiting substances. Tissue-isolated Morris hepatomas (7288CTC) growing in young or adult Buffalo rats were perfused with blood from donor rats. Hyperlipemic blood for perfusion was obtained from 2-day starved tumor-bearing (Buffalo) or non-tumor-bearing (Buffalo or Lewis) rats. At the end of the perfusions the tumors were labeled with a pulse of [3H]thymidine (2 microCi/g estimated tumor wet weight). [3H]Thymidine incorporation in tumors growing in fed adult rats was increased from 80 +/- 5 (SD) dpm/micrograms DNA at zero time (before perfusion) to 209 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Tumors growing in fed or starved young rats showed similar responses, and hyperlipemic blood from non-tumor-bearing rats was as effective as hyperlipemic blood from tumor-bearing rats. Perfusion of tumors growing in starved rats with normolipemic blood from fed adult rats decreased [3H]thymidine incorporation from 211 +/- 13 dpm/micrograms DNA before perfusion to 68 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Cells, plasma, and plasma subfractions from hyperlipemic blood were reconstituted to whole blood using plasma, cells, and whole blood, respectively, from fed rats and the mixtures were perfused into tumors growing in fed adult rats. Mixtures containing hyperlipemic plasma, lipid extracts (ethanol:acetone, 1:1) of hyperlipemic plasma, or albumin from hyperlipemic plasma increased tumor [3H]thymidine incorporation. Free fatty acid concentrations were increased about five times in hyperlipemic plasma and perfusion of tumors with normolipemic blood containing added linoleic and arachid

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Cycloheximide; DNA Replication; Hyperlipidemias; Linoleic Acid; Linoleic Acids; Liver Neoplasms, Experimental; Male; Perfusion; Rats; Rats, Inbred BUF; Rats, Inbred Lew; Thymidine; Tritium

Topics: Carbon Isotopes; Fatty Acids; Glycerides; Heart Diseases; Hyperlipidemias; Hypertriglyceridemia; Linoleic Acid; Lipid Metabolism; Lipids; Lipoproteins; Myocardial Infarction; Palmitates; Palmitic Acid; Tritium

Topics: Butter; Cocos; Dietary Fats; Egg Yolk; Fatty Acids; Fatty Acids, Essential; Hyperlipidemias; Linoleic Acid; Lipids; Oils; Serum

Topics: Adolescent; Carbohydrates; Child; Cholesterol; Fatty Acids; Fatty Acids, Essential; Genetics, Medical; Glycerides; Hyperlipidemias; Hyperlipoproteinemia Type I; Hyperlipoproteinemia Type III; Linoleic Acid; Lipids; Palmitic Acid

Topics: Biomedical Research; Blood Chemical Analysis; Chromatography; Chromatography, Paper; Colorimetry; Fats; Glycerides; Hydroxylamines; Hyperlipidemias; Lecithins; Linoleic Acid; Lipids; Palmitic Acid; Phosphatidylcholines; Research; Triolein

Topics: Animals; Cholesterol; Chromatography; Colorimetry; Glycerides; Hyperlipidemias; Linoleic Acid; Lipids; Liver; Mice; Pharmacology; Polyethylene Glycols; Rats; Research; Surface-Active Agents

Topics: Arteriosclerosis; Atherosclerosis; Dietary Fats; Glycerides; Heparin; Heparinoids; Hypercholesterolemia; Hyperlipidemias; Linoleic Acid; Lipid Metabolism; Lipoprotein Lipase; Niacin