2014年2月
Critical roles of nardilysin in the maintenance of body temperature homoeostasis
NATURE COMMUNICATIONS
- 巻
- 5
- 号
- 開始ページ
- 3224
- 終了ページ
- 3224
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/ncomms4224
- 出版者・発行元
- NATURE PUBLISHING GROUP
Body temperature homoeostasis in mammals is governed centrally through the regulation of shivering and non-shivering thermogenesis and cutaneous vasomotion. Non-shivering thermogenesis in brown adipose tissue (BAT) is mediated by sympathetic activation, followed by PGC-1 alpha induction, which drives UCP1. Here we identify nardilysin (Nrd1 and NRDc) as a critical regulator of body temperature homoeostasis. Nrd1(-/-) mice show increased energy expenditure owing to enhanced BAT thermogenesis and hyperactivity. Despite these findings, Nrd1(-/-) mice show hypothermia and cold intolerance that are attributed to the lowered set point of body temperature, poor insulation and impaired cold-induced thermogenesis. Induction of beta 3-adrenergic receptor, PGC-1 alpha and UCP1 in response to cold is severely impaired in the absence of NRDc. At the molecular level, NRDc and PGC-1 alpha interact and colocalize at the UCP1 enhancer, where NRDc represses PGC-1 alpha activity. These findings reveal a novel nuclear function of NRDc and provide important insights into the mechanism of thermoregulation.
- リンク情報
-
- DOI
- https://doi.org/10.1038/ncomms4224
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/24492630
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926010
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000332665100001&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1038/ncomms4224
- ISSN : 2041-1723
- PubMed ID : 24492630
- PubMed Central 記事ID : PMC3926010
- Web of Science ID : WOS:000332665100001