Meteorin-like Is a Hormone that Regulates Immune-Adipose Interactions to Increase Beige Fat Thermogenesis

被引：752

作者：

Rao, Rajesh R. ^{[1
,2
]}

Long, Jonathan Z. ^{[1
,2
]}

White, James P. ^{[1
,2
]}

Svensson, Katrin J. ^{[1
,2
]}

Lou, Jesse ^{[1
,2
]}

Lokurkar, Isha ^{[1
,2
]}

Jedrychowski, Mark P. ^{[2
]}

Ruas, Jorge L. ^{[3
]}

Wrann, Christiane D. ^{[1
,2
]}

Lo, James C. ^{[1
,2
]}

Camera, Donny M. ^{[4
]}

Lachey, Jenn ^{[6
]}

Gygi, Steven ^{[2
]}

Seehra, Jasbir ^{[6
]}

Hawley, John A. ^{[4
,5
]}

Spiegelman, Bruce M. ^{[1
,2
]}

机构：

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

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

[3] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden

[4] Australian Catholic Univ, Dept Exercise Sci, Exercise & Nutr Res Grp, Fitzroy, Vic 3065, Australia

[5] Liverpool John Moores Univ, Res Inst Sport & Exercise Sci, Liverpool L3 2AJ, Merseyside, England

[6] Ember Therapeut Inc, Watertown, MA 02472 USA

来源：

CELL | 2014年 / 157卷 / 06期

基金：

瑞典研究理事会; 美国国家卫生研究院;

关键词：

SKELETAL-MUSCLE; WHITE FAT; EXERCISE; PGC-1-ALPHA; MACROPHAGES; COACTIVATOR; ACTIVATION; DYSFUNCTION; ADIPOCYTES; PREVENTION;

D O I：

10.1016/j.cell.2014.03.065

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Exercise training benefits many organ systems and offers protection against metabolic disorders such as obesity and diabetes. Using the recently identified isoform of PGC1-alpha (PGC1-alpha 4) as a discovery tool, we report the identification of meteorin-like (Metrnl), a circulating factor that is induced in muscle after exercise and in adipose tissue upon cold exposure. Increasing circulating levels of Metrnl stimulates energy expenditure and improves glucose tolerance and the expression of genes associated with beige fat thermogenesis and anti-inflammatory cytokines. Metrnl stimulates an eosinophil-dependent increase in IL-4 expression and promotes alternative activation of adipose tissue macrophages, which are required for the increased expression of the thermogenic and anti-inflammatory gene programs in fat. Importantly, blocking Metrnl actions in vivo significantly attenuates chronic cold-exposure-induced alternative macrophage activation and thermogenic gene responses. Thus, Metrnl links host-adaptive responses to the regulation of energy homeostasis and tissue inflammation and has therapeutic potential for metabolic and inflammatory diseases.

引用

页码：1279 / 1291

页数：13

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