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SummaryWe compared the efficacy of alpha-linolenic acid (a-LNA, n-3) and linoleic acid (LA, n-6) on orotic acid (OA)-induced fatty liver in Sprague-Dawley rats. Rats were fed semi-synthetic diets containing either LA or a-LNA with or without 1% OA for 2wk. OA supplementation lowered serum lipids in LA+OA groups. In addition to the decline of serum lipids in a-LNA groups compared to LA groups, a further decrease was found in a-LNA+OA groups compared to LA+OA groups. OA-containing diets significantly increased the liver weights and triacylglycerol (TG) accumulations compared with the OA-free diets. These results were attributed to the significant increases in the activities of phosphatidate phos phohydrolase (PAP), a rate-limiting enzyme of TG synthesis, and glucose-6-phosphate dehy drogenase, a fatty acid synthesis-related enzyme. However, the increase of PAP activity was significantly less in the a-LNA+OA group as compared with the LA+OA group. These results suggest that dietary a-LNA alleviates OA-induced hepatic TG accumulation through the attenuation of hepatic TG synthesis in rats.

Conjugated linoleic acid (CLA) is known to modulate lipid and lipoprotein metabolism. We examined the effects of dietary CLA (1 and 2%) on hepatic microsomal triacylglycerol transfer protein (MTP) activity, known to be essential for the assembly/secretion of the apolipoprotein B-containing lipoproteins, and lipid concentrations of liver and plasma in OLETF obese rats. A significant reduction in hepatic MTP activity in CLA-fed rats in comparison to rats fed a linoleic acid (LA) diet was noted. Hepatic and serum triacylglycerol (TAG) concentrations were lowered in the CLA groups as compared to the control LA group. Decreased serum insulin and leptin levels were seen in the CLA groups. These results indicate that dietary CLA reduces both hepatic MTP activity and TAG content, and therefore reduces hepatic lipoprotein assembly and secretion.