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Alpha‐lipoic acid protects against weight gain and hyperlipidemia in response to high fat feeding in obese Zucker rats

Alpha‐lipoic acid (ALA) supplementation has recently been shown to have anti‐obesity and lipid‐lowering properties, however, the underlying molecular mechanisms are unknown. Our objectives were to examine the effects of ALA supplementation on body weight, blood lipids, and hepatic lipogenic response in obese Zucker rats. Rats (n=8) were randomly assigned to either a Western Diet (WD) or a WD supplemented with 0.25% ALA. Feed intake was matched between the two groups. ALA protected (p=0.01) against diet‐induced obesity (102.5±3.1 vs. 121.5± 3.6, % change BW) and reduced (p<0.05) plasma total cholesterol (11%), non‐HDL cholesterol (25%), and total LDL particle number (46%) compared with the WD group. Plasma triglycerides (TAG) were increased (p=0.09) in response to ALA supplementation, largely due to an increase in VLDL/chylomicron particle number compared with the WD group. Hepatic TAG (mmol/g tissue) was reduced (p<0.05) by 46% in the ALA group compared with the WD animals. ALA supplementation reduced the mRNA expression of hepatic acetyl‐CoA carboxylase (2.4 fold, p=0.03) and fatty acid synthase (5.4 fold, p=0.02) compared with the WD group. FAS protein abundance was also decreased (43%) in the ALA group compared with the WD group. These data suggest that ALA supplementation protects against diet‐induced weight gain and dyslipidemia by modulating hepatic lipogenesis.