Alpha-Lipoic Acid Protects Against Weight Gain and Modulates Hepatic Lipid Response to High Fat Feeding in Obese Zucker Rats
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Alpha-lipoic acid (R+ isomer, LA) has recently been shown to have anti-obesity and lipid-lowering properties; however, the underlying molecular mechanisms have not been fully elucidated. Our objectives were to examine the effects of LA supplementation on body weight (BW) and blood and tissue lipid profiles in obese Zucker rats fed a high fat (HF, 41% energy) diet. Rats (n=8/group) were randomly assigned to the HF diet or the HF diet supplemented with 0.25% LA (HF-LA) for 30 days. Feed and caloric intake was matched between the two groups to remove confounding responses associated with the anorectic effects of LA. The HF-LA group was protected ( p <0.05) against diet-induced obesity (102.5±3.1 vs. 121.5± 3.6, % change BW) and demonstrated a reduction in plasma total cholesterol (11%, p <0.05), non-HDL cholesterol (25%, p =0.1) and total LDL particle number (46%) compared with the HF group. Plasma triglycerides (TG) were non-significantly increased ( p =0.1) in response to LA supplementation, largely due to increased VLDL particles (160%) compared with the HF group. LA supplementation reduced (46%, p <0.05) hepatic TG and differentially modulated hepatic fatty acids by increasing ( p <0.05) myristic, linoleic, and archidonic and reducing palmitic and palmitoleic concentrations compared with the HF group. LA supplementation reduced ( p <0.05) the mRNA expression and protein abundance of hepatic acetyl-CoA carboxylase (∼0.4 and 0.5 fold, respectively) and fatty acid synthase (∼ 0.18 and 0.46 fold, respectively) compared with the HF group. LA supplementation also increased ( p <0.05) carnitine palmitoyltransferase I mRNA expression (1.9 fold) and protein abundance (2.1 fold) compared with the HF animals. These data suggest that LA supplementation protects against diet-induced weight gain and modulates hepatic lipid metabolism on a fat diet.