| First Author | Lee B | Year | 2022 |
| Journal | Exp Mol Med | Volume | 54 |
| Issue | 11 | Pages | 2036-2046 |
| PubMed ID | 36434042 | Mgi Jnum | J:332205 |
| Mgi Id | MGI:7411719 | Doi | 10.1038/s12276-022-00888-9 |
| Citation | Lee B, et al. (2022) SMP30-mediated synthesis of vitamin C activates the liver PPARalpha/FGF21 axis to regulate thermogenesis in mice. Exp Mol Med 54(11):2036-2046 |
| abstractText | 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 PPARalpha to upregulate FGF21. Our findings demonstrate that SMP30-mediated synthesis of vitamin C activates the PPARalpha/FGF21 axis, contributing to the maintenance of thermogenesis in mice. |
