Critical roles of nardilysin in the maintenance of body temperature homoeostasis.

• Hiraoka, Yoshinori

• Matsuoka, Tatsuhiko

• Ohno, Mikiko

• Nakamura, Kazuhiro

• Saijo, Sayaka

• Matsumura, Shigenobu

• Nishi, Kiyoto

• Sakamoto, Jiro

• Chen, Po-Min

• Inoue, Kazuo

• Fushiki, Tohru

• Kita, Toru

• Kimura, Takeshi

• Nishi, Eiichiro

Abstract

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-1α 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 β3-adrenergic receptor, PGC-1α and UCP1 in response to cold is severely impaired in the absence of NRDc. At the molecular level, NRDc and PGC-1α interact and co-localize at the UCP1 enhancer, where NRDc represses PGC-1α activity. These findings reveal a novel nuclear function of NRDc and provide important insights into the mechanism of thermoregulation.

Journal

• Nature communications

  Nature communications 5 2014-02-04

  Nature Publishing Group

Keywords

• Biological sciences
• Medical research

Details

• CRID: 1050001335780695808
• NII Article ID: 120005367798
• ISSN: 20411723
• HANDLE: 2433/180643
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles