Mitochondrial biogenesis in white adipose tissue mediated by JMJD1A-PGC-1 axis limits age-related metabolic disease

Autor: Ryo Ito, Shiyu Xie, Myagmar Tumenjargal, Yuto Sugahara, Chaoran Yang, Hiroki Takahashi, Makoto Arai, Shin-Ichi Inoue, Aoi Uchida, Kenji Nakano, Hyunmi Choi, Ge Yang, Yanan Zhao, Rei Yamaguchi, Hitomi Jin, Hina Sagae, Youichiro Wada, Toshiya Tanaka, Hiroshi Kimura, Tatsuhiko Kodama, Hiroyuki Aburatani, Kazuhisa Takeda, Takeshi Inagaki, Timothy F. Osborne, Takeshi Yoneshiro, Yoshihiro Matsumura, Juro Sakai
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 4, Pp 109398- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109398
Popis: Summary: Mitochondria play a vital role in non-shivering thermogenesis in both brown and subcutaneous white adipose tissues (BAT and scWAT, respectively). However, specific regulatory mechanisms driving mitochondrial function in these tissues have been unclear. Here we demonstrate that prolonged activation of β-adrenergic signaling induces epigenetic modifications in scWAT, specifically targeting the enhancers for the mitochondria master regulator genes Pgc1a/b. This is mediated at least partially through JMJD1A, a histone demethylase that in response to β-adrenergic signals, facilitates H3K9 demethylation of the Pgc1a/b enhancers, promoting mitochondrial biogenesis and the formation of beige adipocytes. Disruption of demethylation activity of JMJD1A in mice impairs activation of Pgc1a/b driven mitochondrial biogenesis and limits scWAT beiging, contributing to reduced energy expenditure, obesity, insulin resistance, and metabolic disorders. Notably, JMJD1A demethylase activity is not required for Pgc1a/b dependent thermogenic capacity of BAT especially during acute cold stress, emphasizing the importance of scWAT thermogenesis in overall energy metabolism.
Databáze: Directory of Open Access Journals