Critical roles of nardilysin in the maintenance of body temperature homoeostasis

被引：38

作者：

Hiraoka, Yoshinori ^{[1
]}

Matsuoka, Tatsuhiko ^{[1
]}

Ohno, Mikiko ^{[1
]}

Nakamura, Kazuhiro ^{[2
]}

Saijo, Sayaka ^{[1
]}

Matsumura, Shigenobu ^{[3
]}

Nishi, Kiyoto ^{[1
]}

Sakamoto, Jiro ^{[1
]}

Chen, Po-Min ^{[1
]}

Inoue, Kazuo ^{[3
]}

Fushiki, Tohru ^{[3
]}

Kita, Toru ^{[4
]}

Kimura, Takeshi ^{[1
]}

Nishi, Eiichiro ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Sakyo Ku, Kyoto 6068507, Japan

[2] Kyoto Univ, Career Path Promot Unit Young Life Scientists, Sakyo Ku, Kyoto 6068501, Japan

[3] Kyoto Univ, Grad Sch Agr, Div Food Sci & Biotechnol, Nutr Chem Lab,Sakyo Ku, Kyoto 6068502, Japan

[4] Kobe City Med Ctr Gen Hosp, Chuo Ku, Kobe, Hyogo 6500046, Japan

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

BROWN ADIPOSE-TISSUE; ARGININE DIBASIC CONVERTASE; DIET-INDUCED THERMOGENESIS; UNCOUPLING PROTEIN; GROWTH-FACTOR; CELL-LINE; RECEPTOR; MICE; EXPRESSION; OBESITY;

D O I：

10.1038/ncomms4224

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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