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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2036-2046
Number of pages11
JournalExperimental and Molecular Medicine
Volume54
Issue number11
DOIs
Publication statusPublished - Nov 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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