Physiological activities of the combination of fish oil and α-lipoic acid affecting hepatic lipogenesis and parameters related to oxidative stress in rats

Purpose We studied the combined effect of fish oil and alpha-lipoic acid on hepatic lipogenesis and fatty acid oxidation and parameters of oxidative stress in rats fed lipogenic diets high in sucrose. A control diet contained a saturated fat (palm oil) that gives high rate of hepatic lipogenesis. Methods Male Sprague-Dawley rats were fed diets supplemented with 0 or 2.5 g/kg alpha-lipoic acid and containing 0, 20, or 100 g/kg fish oil, for 21 days. Results alpha-Lipoic acid significantly reduced food intake during 0-8 days but not the later period of the experiment. Fish oil and alpha-lipoic acid decreased serum lipid concentrations and their combination further decreased the parameters in an additive fashion. The combination of fish oil and alpha-lipoic acid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Fish oil increased the parameters of hepatic fatty acid oxidation enzymes. alpha-Lipoic acid appeared to antagonize the stimulating effects of fish oil of fatty acid oxidation through reductions in the activity of some fatty acid oxidation enzymes. alpha-Lipoic acid attenuated fish oil-dependent increases in serum and liver malondialdehyde levels, and this compound also reduced the serum 8-hydroxy2'-deoxyguanosine level. alpha-Lipoic acid affected various parameters related to the antioxidant system; fish oil also affected some of the parameters. Conclusions The combination of fish oil and alpha-lipoic acid effectively reduced serum lipid levels through the additive down-regulation of hepatic lipogenesis. alpha-Lipoic acid was effective in attenuating fish oil-mediated oxidative stress.