SMP30-mediated synthesis of vitamin C activates the liver PPARα/FGF21 axis to regulate thermogenesis in mice

Bonggi Lee, Hye Jin An, Dae Hyun Kim, Min Kyeong Lee, Hyeon Hak Jeong, Ki Wung Chung, Younghoon Go, Arnold Y. Seo, Il Yong Kim, Je Kyung Seong, Byung Pal Yu, Jaewon Lee, Eunok Im, In Kyu Lee, Myung Shik Lee, Ken ichi Yamada, Hae Young Chung

研究成果: ジャーナルへの寄稿学術誌査読

3 被引用数 (Scopus)

抄録

The vitamin-C-synthesizing enzyme senescent marker protein 30 (SMP30) is a cold resistance gene in Drosophila, and vitamin C concentration increases in brown adipose tissue post-cold exposure. However, the roles of SMP30 in thermogenesis are unknown. Here, we tested the molecular mechanism of thermogenesis using wild-type (WT) and vitamin C-deficient SMP30-knockout (KO) mice. SMP30-KO mice gained more weight than WT mice without a change in food intake in response to short-term high-fat diet feeding. Indirect calorimetry and cold-challenge experiments indicated that energy expenditure is lower in SMP30-KO mice, which is associated with decreased thermogenesis in adipose tissues. Therefore, SMP30-KO mice do not lose weight during cold exposure, whereas WT mice lose weight markedly. Mechanistically, the levels of serum FGF21 were notably lower in SMP30-KO mice, and vitamin C supplementation in SMP30-KO mice recovered FGF21 expression and thermogenesis, with a marked reduction in body weight during cold exposure. Further experiments revealed that vitamin C activates PPARα to upregulate FGF21. Our findings demonstrate that SMP30-mediated synthesis of vitamin C activates the PPARα/FGF21 axis, contributing to the maintenance of thermogenesis in mice.

本文言語英語
ページ(範囲)2036-2046
ページ数11
ジャーナルExperimental and Molecular Medicine
54
11
DOI
出版ステータス出版済み - 11月 2022

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子医療
  • 分子生物学
  • 臨床生化学

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