| First Author | Hiraoka Y | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 3224 | PubMed ID | 24492630 |
| Mgi Jnum | J:225248 | Mgi Id | MGI:5691899 |
| Doi | 10.1038/ncomms4224 | Citation | Hiraoka Y, et al. (2014) Critical roles of nardilysin in the maintenance of body temperature homoeostasis. Nat Commun 5:3224 |
| abstractText | 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-1alpha 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 beta3-adrenergic receptor, PGC-1alpha and UCP1 in response to cold is severely impaired in the absence of NRDc. At the molecular level, NRDc and PGC-1alpha interact and co-localize at the UCP1 enhancer, where NRDc represses PGC-1alpha activity. These findings reveal a novel nuclear function of NRDc and provide important insights into the mechanism of thermoregulation. |
