Ascorbic acid inhibits visceral obesity and nonalcoholic fatty liver disease by activating peroxisome proliferator-activated receptor [alpha] 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[alp...

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Bibliographic Details
Published in:International Journal of Obesity 2019-08, Vol.43 (8), p.1620
Main Authors: Lee, Hyunghee, Ahn, Jiwon, Shin, Soon Shik, Yoon, Michung
Format: Article
Language:English
Subjects:
Care and treatment
Fatty liver
Health aspects
Obesity
Physiological aspects
Vitamin C
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Summary: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 HFD 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 HFD-AA-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].
ISSN:0307-0565
1476-5497
DOI:10.1038/s41366-018-0212-0