11-octadecenoic-acid and Non-alcoholic-Fatty-Liver-Disease

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

Elongation of very long chain fatty acid-like family member 6 (ELOVL6) is a fatty acyl elongase that performs the initial and rate-limiting condensing reaction required for microsomal elongation of long-chain fatty acids. Our previous in vitro studies suggested that ELOVL6 elongated long-chain saturated fatty acids and monounsaturated fatty acids with chain lengths of 12 to 16 carbons. Here, we describe the generation and phenotypic characterization of Elovl6(-/-) mice. As predicted from the in vitro studies, livers from Elovl6(-/-) mice accumulated palmitic (C16:0) and palmitoleic (C16:1, n-7) fatty acids and contained significantly less stearic (C18:0) and oleic (C18:1, n-9) acids, confirming that ELOVL6 is the only enzyme capable of elongating palmitate (C16:0). Unexpectedly, Elovl6(-/-) mice produced vaccenic acid (C18:1, n-7), the elongated product of palmitoleate (C16:1, n-7), suggesting that palmitoleate (C16:1, n-7) to vaccenate (C18:1, n-7) elongation was not specific to ELOVL6. The only detected consequence of deleting Elovl6(-/-) in mice was that their livers accumulated significantly more triglycerides than wild-type mice when fed a fat-free/high-carbohydrate diet. When mice were fed a high-fat diet or ELOVL6 was deleted in ob/ob mice, the absence of ELOVL6 did not alter the development of obesity, fatty liver, hyperglycemia, or hyperinsulinemia. Combined, these results suggest that palmitoleic (C16:1, n-7) and vaccenic (C18:1, n-7) acids can largely replace the roles of oleic acid (C18:1, n-9) in vivo and that the deletion of ELOVL6 does not protect mice from the development of hepatic steatosis or insulin resistance.

Topics: Acetyltransferases; Animals; Chimera; Clone Cells; Crosses, Genetic; Diabetes Mellitus, Experimental; Diet, Fat-Restricted; Diet, High-Fat; Dietary Carbohydrates; Embryonic Stem Cells; Fatty Acid Elongases; Gene Knockout Techniques; Insulin Resistance; Liver; Male; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Non-alcoholic Fatty Liver Disease; Obesity; Oleic Acid; Oleic Acids