gamma-linolenic-acid and Fatty-Liver

Triacylglycerol accumulation in the liver (fatty liver) caused by ethanol or carbon tetrachloride involves interactions with essential fatty acids and prostaglandins. The degree to which the fatty liver develops is dependent on total dietary fat intake. Both ethanol and carbon tetrachloride impair desaturation of linoleic acid and dihomo-gamma-linolenic acid and this appears to be relevant to the pathogenesis of fatty liver from two points of view. First, low arachidonic acid in liver phospholipids is associated with increased liver triacylglycerol content whether caused by ethanol, carbon tetrachloride, or essential fatty acid deficiency. Second, essential fatty acids including gamma-linolenic acid and arachidonic acid, as well as the prostaglandins, prevent ethanol- and carbon tetrachloride-induced fatty liver. Arachidonic acid and possibly the prostaglandins are therefore likely to be directly involved in lipoprotein and triacylglycerol secretion by the liver.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acid; Arachidonic Acids; Carbon Tetrachloride; Cricetinae; Dietary Fats; Ethanol; Fatty Acids, Essential; Fatty Liver; Fatty Liver, Alcoholic; gamma-Linolenic Acid; Guinea Pigs; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Liver; Mice; Prostaglandins; Rats; Species Specificity; Triglycerides

Echium oil (EO), which is enriched in 18:4 n-3, the immediate product of fatty acid desaturase 2 (FADS2) desaturation of 18:3 n-3, is as atheroprotective as fish oil (FO). The objective of this study was to determine whether botanical oils enriched in the FADS2 products 18:3 n-6 versus 18:4 n-3 are equally atheroprotective. LDL receptor KO mice were fed one of four atherogenic diets containing 0.2% cholesterol and 10% calories as palm oil (PO) plus 10% calories as: 1) PO; 2) borage oil (BO; 18:3 n-6 enriched); 3) EO (18:4 n-3 enriched); or 4) FO for 16 weeks. Mice fed BO, EO, and FO versus PO had significantly lower plasma total and VLDL cholesterol concentrations; hepatic neutral lipid content and inflammation, aortic CE content, aortic root intimal area and macrophage content; and peritoneal macrophage inflammation, CE content, and ex vivo chemotaxis. Atheromas lacked oxidized CEs despite abundant generation of macrophage 12/15 lipooxygenase-derived metabolites. We conclude that botanical oils enriched in 18:3 n-6 and 18:4 n-3 PUFAs beyond the rate-limiting FADS2 enzyme are equally effective in preventing atherosclerosis and hepatosteatosis compared with saturated/monounsaturated fat due to cellular enrichment of ≥20 PUFAs, reduced plasma VLDL, and attenuated macrophage inflammation.

Topics: Animals; Atherosclerosis; Cholesterol, VLDL; Diet, Atherogenic; Echium; Fatty Acid Desaturases; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Liver; Fish Oils; gamma-Linolenic Acid; Humans; Liver; Mice; Mice, Knockout; Palm Oil; Plant Oils; Receptors, LDL

The present study was done to clarify the mechanism by which conjugated linoleic acid (CLA) induces fatty liver in mice and to attenuate this symptom by adding other dietary fatty acids.. Mice were given CLA short (12 h) or long (4 wk) term or given CLA with linoleic acid (LA) or gamma-linolenic acid (GLA) in the long term (4 wk). Total lipids, triacylglycerol, and prostaglandin E(2) (PGE(2)) levels in the liver were determined.. A single administration of CLA significantly increased PGE(2) levels in the liver 12 h after administration. However, long-term administration of CLA significantly decreased the liver PGE(2) level and induced fatty liver. GLA increased PGE(2) levels, and coadministration with GLA, but not with LA, prevented the CLA-induced fatty liver.. These data suggest that CLA initially stimulates PGE(2) production followed by depletion of PGE(2) sources in the liver. The fatty liver associated with PGE(2) reduction by CLA ingestion can be attenuated by GLA in mice.

Topics: Animals; Dinoprostone; Fatty Liver; gamma-Linolenic Acid; Kinetics; Linoleic Acids, Conjugated; Liver; Male; Mice