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

Nature communications 2014

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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.

Citation

Yoshinori Hiraoka, Tatsuhiko Matsuoka, Mikiko Ohno, Kazuhiro Nakamura, Sayaka Saijo, Shigenobu Matsumura, Kiyoto Nishi, Jiro Sakamoto, Po-Min Chen, Kazuo Inoue, Tohru Fushiki, Toru Kita, Takeshi Kimura, Eiichiro Nishi. Critical roles of nardilysin in the maintenance of body temperature homoeostasis. Nature communications. 2014;5:3224