linoleic-acid and Dyslipidemias

Oxylipins are lipid mediators produced from polyunsaturated fatty acid (PUFA) metabolism, and are thought to be a molecular explanation for the diverse biological effects of PUFAs. Like PUFAs, oxylipins are distinguished by their omega-6 (n6) or omega-3 (n3) chemistry. We review the use of n6 oxylipins as biomarkers of disease and their use in diagnosis and risk assessment. We show cases where oxylipins derived from linoleate (LA) or arachidonate (AA) produced by the activities of lipoxygenase, cyclooxygenase, epoxygenase, ω/ω-1 hydroxylase, and autooxidation are useful as biomarkers or risk markers. HODEs, KODEs, EpOMEs, DiHOMEs, and other metabolites of LA as well as prostanoids, HETEs, KETEs, EpETrEs, and DiHETrEs, and other metabolites of AA were useful for understanding the different signaling environments in conditions from traumatic brain injury, to major coronary events, dyslipidemia, sepsis, and more. We next evaluate interventions that alter the concentrations of n6 oxylipins in plasma. We note the utility and response of each plasma fraction, and the generally increasing utility from the non-esterified, to the esterified, to the lipoprotein fractions. Finally, we review the effects which are specifically related to n6 oxylipins and most likely to be beneficial. Both n6 and n3 oxylipins work together in an exceedingly complex matrix to produce physiological effects. This overview should provide future investigators with important perspectives for the emerging utility of n6 oxylipins as products of n6 PUFAs in human health.

Topics: Biomarkers; Brain Injuries, Traumatic; Coronary Disease; Dietary Supplements; Dyslipidemias; Fatty Acids, Omega-6; Humans; Linoleic Acid; Lipid Metabolism; Lipoxygenase; Oxylipins

The prevalence of obesity and dyslipidemia has increased worldwide. The role of trace elements in the pathogenesis of these conditions is not well understood. This study examines the relationship between dietary zinc (Zn) intake and plasma concentrations of Zn, copper (Cu) and iron (Fe) with lipid profile indicators, fatty acid composition in plasma phospholipids and desaturase enzyme activities in a dyslipidemic population. The role of the newly proposed biomarker of Zn status, the linoleic:dihomo-gama-linolenic acid (LA:DGLA) ratio, in predicting Zn status of dyslipidemic subjects has been explored. The study included 27 dyslipidemic adults, 39-72 years old. Trace elements were determined using atomic absorption spectrometry and fatty acid composition by a liquid gas chromatography. Desaturase activities were calculated from product-precursor fatty acid ratios. Dietary data were obtained using 24 h recall questionnaires. Insufficient dietary intake of Zn, low plasma Zn concentrations and an altered Cu:Zn ratio is related to modified fatty acid profile in subjects with dyslipidemia. Plasma Zn status was associated with obesity. There was no correlation between dietary Zn intake and plasma Zn status. The LA:DGLA ratio was inversely linked to dietary Zn intake. Cu, in addition to Zn, may directly or indirectly, affect the activity of desaturase enzymes.

Topics: Adult; Aged; Biomarkers; Copper; Cross-Sectional Studies; Dyslipidemias; Fatty Acid Desaturases; Fatty Acids; Feeding Behavior; Female; gamma-Linolenic Acid; Humans; Iron; Linoleic Acid; Male; Middle Aged; Nutritional Status; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Zinc

In the present study, we investigated the impact of substituting alpha-linolenic acid (ALA) or long-chain n-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) for linoleic acid and hence decreasing n-6:n-3 PUFA ratio on high-fructose diet-induced hypertriglyceridemia and associated hepatic changes. Weanling male Wistar rats were divided into four groups and fed with starch-diet (n-6:n-3 PUFA ratio 215:1) and high-fructose diets with different n-6:n-3 PUFA ratio (215:1, 2:1 with ALA and 5:1 with long-chain n-3 PUFA) for twenty-four weeks. Substitution of linoleic acid with ALA (n-6:n-3 PUFA ratio of 2) or long-chain n-3 PUFA (n-6:n-3 PUFA ratio of 5) protected the rats from fructose-induced dyslipidemia, hepatic oxidative stress and corrected lipogenic and proinflammatory gene expression. Both ALA and long-chain n-3 PUFA supplementation also reversed the fructose-induced upregulation of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene, which is involved in the generation of active glucocorticoids in tissues. Although both ALA and LC n-3 PUFA prevented fructose-induced dyslipidemia to a similar extent, compared to ALA, LC n-3 PUFA is more effective in preventing hepatic oxidative stress and inflammation.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; alpha-Linolenic Acid; Animals; Diet; Dyslipidemias; Fructose; Gene Expression Regulation; Inflammation; Linoleic Acid; Liver; Male; Oxidative Stress; Rats; Rats, Wistar

Data on intake of oleic acid (OA) and insulin resistance (IR) are inconsistent. We investigated whether OA in serum phosphatidylcholine relates to surrogate measures of IR in dyslipidaemic subjects from a Mediterranean population.. Cross-sectional study of 361 non-diabetic subjects (205 men, 156 women; mean age 44 and 46 y, respectively; BMI 25.7 kg/m(2)). IR was diagnosed by BMI and HOMA values using published criteria validated against the euglycemic clamp. Alternatively, IR was defined by the 75th percentile of HOMA-IR of our study population. The fatty acid composition of serum phosphatidylcholine was determined by gas-chromatography.. The mean (±SD) proportion of OA was 11.7 ± 2.0%. Ninety-two subjects (25.5%) had IR. By adjusted logistic regression, including the proportions of other fatty acids known to relate to IR, the odds ratios (OR) (95% confidence intervals) for IR were 0.75 (0.62-0.92) for 1% increase in OA and 0.84 (0.71-0.99) for 1% increase in linoleic acid. Other fatty acids were unrelated to IR. When using the alternate definition of IR, OA remained a significant predictor (0.80 [0.65-0.99]).. Higher phospholipid proportions of OA relate to less IR, suggesting an added benefit of increasing olive oil intake within the Mediterranean diet.

Topics: Adult; Biomarkers; Body Mass Index; Cross-Sectional Studies; Diet, Mediterranean; Dyslipidemias; Female; Fruit; Glucose Clamp Technique; Humans; Insulin Resistance; Linoleic Acid; Male; Middle Aged; Olea; Oleic Acid; Olive Oil; Phosphatidylcholines; Phospholipids; Plant Oils; Spain

Studies on conjugated linoleic acid ingestion and its effect on cardiac tissue are necessary for the safe utilization of this compound as supplement for weight loss. Male Wistar 24-rats were divided into four groups (n=6):(C)given standard chow, water and 0.5 ml saline, twice a week by gavage; (C-CLA)receiving standard chow, water and 0.5 ml of conjugated linoleic acid, twice a week, by gavage; (S)given standard chow, saline by gavage, and 30% sucrose in its drinking water; (S-CLA)receiving standard chow, 30% sucrose in its drinking water and conjugated linoleic acid. After 42 days of treatment S rats had obesity with increased abdominal-circumference, dyslipidemia, oxidative stress and myocardial lower citrate synthase(CS) and higher lactate dehydrogenase(LDH) activities than C. Conjugated linoleic acid had no effects on morphometric parameters in C-CLA, as compared to C, but normalized morphometric parameters comparing S-CLA with S. There was a negative correlation between abdominal adiposity and resting metabolic rate. Conjugated linoleic acid effect, enhancing fasting-VO(2)/surface area, postprandial-carbohydrate oxidation and serum lipid hydroperoxide resembled to that of the S group. Conjugated linoleic acid induced cardiac oxidative stress in both fed conditions, and triacylglycerol accumulation in S-CLA rats. Conjugated linoleic acid depressed myocardial LDH comparing C-CLA with C, and beta-hydroxyacyl-coenzyme-A dehydrogenase/CS ratio, comparing S-CLA with S. In conclusion, dietary conjugated linoleic acid supplementation for weight loss can have long-term effects on cardiac health. Conjugated linoleic acid, isomers c9, t11 and t10, c12c9,t11" and "t10,c12" were changed to "c9, t11" and "t10, c12", respectively. Please check if appropriate.--> presented undesirable pro-oxidant effect and induced metabolic changes in cardiac tissue. Nevertheless, despite its effect on abdominal adiposity in sucrose-rich diet condition, conjugated linoleic acid may be disadvantageous because it can lead to oxidative stress and dyslipidemic profile.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Abdominal Fat; Animals; Citrate (si)-Synthase; Dietary Sucrose; Dyslipidemias; Energy Metabolism; Isomerism; L-Lactate Dehydrogenase; Linoleic Acid; Male; Obesity; Oxidants; Oxidative Stress; Rats; Rats, Wistar

The dyslipidemia of insulin resistance, with high levels of albumin-bound fatty acids, is a strong cardiovascular disease risk. Human arterial smooth muscle cell (hASMC) matrix proteoglycans (PGs) contribute to the retention of apoB lipoproteins in the intima, a possible key step in atherogenesis. We investigated the effects of high NEFA levels on the PGs secreted by hASMCs and whether these effects might alter the PG affinity for low-density lipoprotein.. hASMC exposed for 72 hours to high concentrations (800 micromol/L) of linoleate (LO) or palmitate upregulated the core protein mRNAs of the major PGs, as measured by quantitative PCR. Insulin (1 nmol/L) and the PPARgamma agonist rosiglitazone (10 micromol/L) blocked these effects. In addition, high LO increased the mRNA levels of enzymes required for glycosaminoglycan (GAG) synthesis. Exposure to NEFA increased the chondroitin sulfate:heparan sulfate ratio and the negative charge of the PGs. Because of these changes, the GAGs secreted by LO-treated cells had a higher affinity for human low-density lipoprotein than GAGs from control cells. Insulin and rosiglitazone inhibited this increase in affinity.. The response of hASMC to NEFA could induce extracellular matrix alterations favoring apoB lipoprotein deposition and atherogenesis.

Topics: Arteries; Atherosclerosis; Cells, Cultured; Chondroitin Sulfate Proteoglycans; Dyslipidemias; Glycosyltransferases; Humans; Hypoglycemic Agents; Insulin; Lectins, C-Type; Linoleic Acid; Lipoproteins, LDL; Muscle, Smooth, Vascular; Palmitates; Proteoglycans; RNA, Messenger; Sulfates; Sulfotransferases; Triglycerides; Versicans