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

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_name

Nat Commun

journal_title

Nature communications

authors

Hiraoka Y,Matsuoka T,Ohno M,Nakamura K,Saijo S,Matsumura S,Nishi K,Sakamoto J,Chen PM,Inoue K,Fushiki T,Kita T,Kimura T,Nishi E

doi

10.1038/ncomms4224

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

3224

issn

2041-1723

pii

ncomms4224

journal_volume

5

pub_type

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