11-octadecenoic-acid and Disease-Models--Animal

Conjugated Linoleic Acids (CLA) are of great interest for analysts since techniques have been developed to determine the dietary occurrence of CLA with a good accuracy. CLA is found in animal products from ruminant sources as the result of biohydrogenation of polyunsaturated fatty acids in the rumen and as the consequence of the delta-9 desaturation of vaccenic acid in animal tissues. CLA can also be obtained in the laboratory by isomerisation of linoleic acid or by total chemical synthesis. While the "natural" isomer is rumenic acid (9c,11t-18:2), synthetic mixtures contain mainly two isomers: the 9c,11t- and the 10t,12c-18:2. Although CLA have been shown to be metabolized into desaturated and chain elongated products, it remains unclear whether these so-formed conjugated metabolites may be involved in the effects of CLA on fatty acid metabolism. Experiments carried out on animal models with CLA have shown different health benefits: anticarcinogenic, antiatherosclerotic effects, modulation of body composition , the "natural" CLA (9c,11t-18:2) being closely related to the protection against cancer and the 10t,12c-18:2 to the reduction of the fat mass. Nevertheless, recent findings have suggested adverse effects in mice. Most of the studies carried out on humans concern the influence of CLA on body composition and its possible inverse association with cancer. Since the results are still controversial and since very few data dealing with the safety of using CLA in long term feeding studies have so far been published, further works are warranted to consider the benefits of CLA for humans.

Topics: Animals; Arteriosclerosis; Body Composition; Disease Models, Animal; Humans; Linoleic Acid; Linoleic Acids, Conjugated; Neoplasms; Oleic Acids; Trans Fatty Acids

Vaccenic acid (VA), the predominant ruminant-derivedtransfat in the food chain, ameliorates hyperlipidemia, yet mechanisms remain elusive. We investigated whether VA could influence tissue endocannabinoids (ECs) by altering the availability of their biosynthetic precursor, arachidonic acid (AA), in membrane phospholipids (PLs). JCR:LA-cprats were assigned to a control diet with or without VA (1% w/w),cis-9,trans-11 conjugated linoleic acid (CLA) (1% w/w) or VA+CLA (1% + 0.5% w/w) for 8 weeks. VA reduced the EC, 2-arachidonoylglycerol (2-AG), in the liver and visceral adipose tissue (VAT) relative to control diet (P< 0.001), but did not change AA in tissue PLs. There was no additive effect of combining VA+CLA on 2-AG relative to VA alone (P> 0.05). Interestingly, VA increased jejunal concentrations of anandamide and those of the noncannabinoid signaling molecules, oleoylethanolamide and palmitoylethanolamide, relative to control diet (P< 0.05). This was consistent with a lower jejunal protein abundance (but not activity) of their degrading enzyme, fatty acid amide hydrolase, as well as the mRNA expression of TNFα and interleukin 1β (P< 0.05). The ability of VA to reduce 2-AG in the liver and VAT provides a potential mechanistic explanation to alleviate ectopic lipid accumulation. The opposing regulation of ECs and other noncannabinoid lipid signaling molecules by VA suggests an activation of benefit via the EC system in the intestine.

Topics: Amidohydrolases; Animals; Anti-Inflammatory Agents; Arachidonic Acids; Caco-2 Cells; Cytokines; Dietary Supplements; Disease Models, Animal; Endocannabinoids; Ethanolamines; Gene Expression Regulation, Enzymologic; Humans; Inflammation; Intestinal Mucosa; Intestines; Intra-Abdominal Fat; Liver; Male; Membrane Lipids; Metabolic Syndrome; Oleic Acids; Polyunsaturated Alkamides; Rats; RNA, Messenger

Trans11-18:1 (vaccenic acid, VA) is one of the most predominant naturally occurring trans fats in our food chain and has recently been shown to exert hypolipidemic effects in animal models. In this study, we reveal new mechanism(s) by which VA can alter body fat distribution, energy utilization and dysfunctional lipid metabolism in an animal model of obesity displaying features of the metabolic syndrome (MetS). Obese JCR:LA-cp rats were assigned to a control diet that included dairy-derived fat or the control diet supplemented with 1% VA. VA reduced total body fat (-6%), stimulated adipose tissue redistribution [reduced mesenteric fat (-17%) while increasing inguinal fat mass (29%)] and decreased adipocyte size (-44%) versus control rats. VA supplementation also increased metabolic rate (7%) concomitantly with an increased preference for whole-body glucose utilization for oxidation and increased insulin sensitivity [lower HOMA-IR (-59%)]. Further, VA decreased nonalcoholic fatty liver disease activity scores (-34%) and reduced hepatic (-27%) and intestinal (-39%) triglyceride secretion relative to control diet, while exerting differential transcriptional regulation of SREBP1 and FAS amongst other key genes in the liver and the intestine. Adding VA to dairy fat alleviates features of MetS potentially by remodeling adipose tissue and attenuating ectopic lipid accumulation in a rat model of obesity and MetS. Increasing VA content in the diet (naturally or by fortification) may be a useful approach to maximize the health value of dairy-derived fats.

Topics: Adipocytes; Adipose Tissue; Animals; Dairy Products; Dietary Fats; Disease Models, Animal; Disease Progression; Fatty Acids; Insulin; Insulin Resistance; Liver; Male; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Oleic Acids; Rats

Evidence suggests a neutral to beneficial role of certain trans fatty acids (TFA) from natural ruminant sources. Trans11-18:1 (vaccenic acid, VA), the most predominant ruminant TFA and a precursor to conjugated linoleic acid, has been shown to improve atherogenic dyslipidemia and symptoms of hepatic steatosis in animal models. The objective of this study was to assess the intestinal bioavailability of various VA sources including synthetic free fatty acid (FFA) and natural ruminant triglyceride forms, as well as the mechanistic pathways that mediate VA's bioactivity.. VA acts as a partial agonist to both peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ in vitro, with similar affinity compared to commonly known PPAR agonists. It was further confirmed that VA at 30 and 100 μM concentrations suppressed cardiomyocyte hypertrophy vitro in a PPAR-α- and PPAR-γ-dependent manner. In vivo, feeding of VA (1%, w/w) resulted in increased mRNA and protein expression of PPAR-γ in the mucosa of JCR:LA-cp rats, a model of the metabolic syndrome (p < 0.01 and p < 0.05, respectively) compared to control. In addition, VA from a triglyceride source had greater intestinal bioavailability in vivo compared to VA provided in an FFA form (p < 0.01).. The activation of PPAR-α- and PPAR-γ-dependent pathways provides a mechanistic explanation of how VA improves blood lipids and related metabolic disorders during conditions of hyperlipidemia. This report also supports the consideration of differential reporting of industrially produced versus natural TFA on food nutrient labels.

Topics: Animals; Binding Sites; Binding, Competitive; Disease Models, Animal; Dyslipidemias; Fatty Acids; Gene Expression Regulation; Intestinal Absorption; Intestinal Mucosa; Lipid Metabolism; Liver; Male; Mesentery; Metabolic Syndrome; Myocytes, Cardiac; Oleic Acids; PPAR alpha; PPAR gamma; Rats; Rats, Inbred Strains

This study assessed the long-term effects of dietary vaccenic acid (VA) and elaidic acid (EA) on plasma and splenocyte phospholipid (PL) composition and related changes in inflammation and splenocyte phenotypes and cytokine responses in obese/insulin resistant JCR:LA-cp rats. Relative to lean control (Ctl), obese Ctl rats had higher serum haptoglobin and impaired T-cell-stimulated cytokine responses. VA and EA diets improved T-cell-stimulated cytokine production; but, only VA normalized serum haptoglobin. However, EA- and VA-fed rats had enhanced LPS-stimulated cytokine responses. The changes elicited by VA were likely due changes in essential fatty acid composition in PL; whereas EA-induced changes may due to direct incorporation into membrane PL.

Topics: Animals; Case-Control Studies; Cytokines; Diet; Disease Models, Animal; Fatty Acids; Haptoglobins; Insulin Resistance; Mitogens; Obesity; Oleic Acid; Oleic Acids; Phospholipids; Rats; Spleen