A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis

被引：3911

作者：

Bostroem, Pontus ^{[1
]}

Wu, Jun ^{[1
]}

Jedrychowski, Mark P. ^{[2
]}

Korde, Anisha ^{[1
]}

Ye, Li ^{[1
]}

Lo, James C. ^{[1
]}

Rasbach, Kyle A. ^{[1
]}

Bostroem, Elisabeth Almer ^{[3
]}

Choi, Jang Hyun ^{[1
]}

Long, Jonathan Z. ^{[1
]}

Kajimura, Shingo ^{[4
,5
]}

Zingaretti, Maria Cristina ^{[6
]}

Vind, Birgitte F. ^{[7
]}

Tu, Hua ^{[8
]}

Cinti, Saverio ^{[6
]}

Hojlund, Kurt ^{[7
]}

Gygi, Steven P. ^{[2
]}

Spiegelman, Bruce M. ^{[1
]}

机构：

[1] Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Div Renal, Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA

[6] Univ Politecn Marche, Dept Expt & Clin Med, Azienda Osped Riuniti, Electron Microscopy Unit, I-60020 Ancona, Italy

[7] Odense Univ Hosp, Diabet Res Ctr, Dept Endocrinol, DK-5000 Odense, Denmark

[8] LakePharma Inc, Belmont, CA 94002 USA

来源：

NATURE | 2012年 / 481卷 / 7382期

基金：

美国国家卫生研究院;

关键词：

SKELETAL-MUSCLE; EXERCISE; PGC-1-ALPHA; PROTECTS; PHOSPHORYLATION; COACTIVATOR; EXPRESSION; MYOBLAST; SWITCH; ROLES;

D O I：

10.1038/nature10777

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：

Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-gamma co-activator-1 alpha (PGC1-alpha). Here we show in mouse that PGC1-alpha expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.

引用

页码：463 / U72

页数：7

共 26 条

[1] Duration of Expression and Activity of Sleeping Beauty Transposase in mouse liver following hydrodynamic DNA delivery [J].