한빛사 논문
Bonggi Lee1,14, Hye Jin An2,14, Dae Hyun Kim2,3, Min-Kyeong Lee1, Hyeon Hak Jeong4, Ki Wung Chung2, Younghoon Go5, Arnold Y. Seo6, Il Yong Kim7,8, Je Kyung Seong7,8,9, Byung Pal Yu10, Jaewon Lee2,3, Eunok Im2,3, In-Kyu Lee11, Myung-Shik Lee12, Ken-ichi Yamada13 and Hae Young Chung2,3
1Department of Food Science and Nutrition, Pukyong National University, Daeyeon-dong, Nam-gu, Busan, South Korea.
2Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, South Korea.
3Molecular Inflammation Research Center for Ageing Intervention (MRCA), Pusan National University, Busan 46241, South Korea.
4Department of Smart Green Technology Engineering, Pukyong National University, Daeyeon-dong, Nam-gu, Busan 48513, South Korea.
5Korean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu, South Korea.
6Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
7Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, and BK21 Plus Program for Creative Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
8Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea.
9Interdisciplinary Program for Bioinformatics, Program for Cancer Biology and BIO-MAX Institute, Seoul National University, Seoul, South Korea.
10Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
11Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea.
12Severance Biomedical Science Institute and Department of Internal Medicine Yonsei University College of Medicine, Seoul, South Korea.
13Department of Bio-functional Science, Kyushu University, Fukuoka, Japan.
14These authors contributed equally: Bonggi Lee, Hye Jin An.
These authors contributed equally: Bonggi Lee, Hye Jin An.
Corresponding author: Correspondence to Hae Young Chung.
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.
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기