Ascorbic acid inhibits visceral obesity and nonalcoholic fatty liver disease by activating peroxisome proliferator-activated receptor α in high-fat-diet-fed C57BL/6J mice

Background/objectives: Ascorbic acid is a known cofactor in the biosynthesis of carnitine, a molecule that has an obligatory role in fatty acid oxidation. Our previous studies have demonstrated that obesity is regulated effectively through peroxisome proliferator-activated receptor alpha (PPAR alpha)-mediated fatty acid beta-oxidation. Thus, this study aimed to determine whether ascorbic acid can inhibit obesity and nonalcoholic fatty liver disease (NAFLD) in part through the actions of PPAR alpha. Design: After C57BL/6J mice received a low-fat diet (LFD, 10% kcal fat), a high-fat diet (HFD, 45% kcal fat), or the same HFD supplemented with ascorbic acid (1% w/w) (HFD-AA) for 15 weeks, variables and determinants of visceral obesity and NAFLD were examined using metabolic measurements, histology, and gene expression. Results: Compared to HFD-fed obese mice, administration of HFD-AA to obese mice reduced body weight gain, visceral adipose tissue mass, and visceral adipocyte size without affecting food consumption profiles. Concomitantly, circulating ascorbic acid concentrations were significantly higher in HFD-AA mice than in RFD mice. Ascorbic acid supplementation increased the mRNA levels of PPAR alpha and its target enzymes involved in fatty acid beta-oxidation in visceral adipose tissues. Consistent with the effects of ascorbic acid on visceral obesity, ascorbic acid not only inhibited hepatic steatosis but also increased the mRNA levels of PPAR alpha-dependent fatty acid beta-oxidation genes in livers. Similarly, hepatic inflammation, fibrosis, and apoptosis were also decreased during ascorbic acid-induced inhibition of visceral obesity. In addition, serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, and LDL cholesterol were lower in HFDAA-fed mice than in those of HFD-fed mice. Conclusions: These results suggest that ascorbic acid seems to suppress HFD-induced visceral obesity and NAFLD in part through the activation of PPAR alpha.