Irisin and FGF21 Are Cold-Induced Endocrine Activators of Brown Fat Function in Humans

被引：811

作者：

Lee, Paul ^{[1
]}

Linderman, Joyce D. ^{[1
]}

Smith, Sheila ^{[1
]}

Brychta, Robert J. ^{[1
]}

Wang, Juan ^{[1
]}

Idelson, Christopher ^{[1
]}

Perron, Rachel M. ^{[1
]}

Werner, Charlotte D. ^{[1
]}

Phan, Giao Q. ^{[2
]}

Kammula, Udai S. ^{[2
]}

Kebebew, Electron ^{[3
]}

Pacak, Karel ^{[4
,5
]}

Chen, Kong Y. ^{[1
]}

Celi, Francesco S. ^{[1
]}

机构：

[1] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA

[2] NIH, Surg Branch, Bethesda, MD 20892 USA

[3] NIH, Endocrine Oncol Branch, Bethesda, MD 20892 USA

[4] NCI, NIH, Bethesda, MD 20892 USA

[5] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA

来源：

CELL METABOLISM | 2014年 / 19卷 / 02期

基金：

英国医学研究理事会;

关键词：

GROWTH-FACTOR; 21; ADIPOSE-TISSUE; ADULT HUMANS; EXERCISE; THERMOGENESIS; ADIPOCYTES; EXPRESSION; EXPOSURE; DISTINCT; REVEALS;

D O I：

10.1016/j.cmet.2013.12.017

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Rediscovery of cold-activated brown adipose tissue (BAT) in humans has boosted research interest in identifying BAT activators for metabolic benefits. Of particular interest are cytokines capable of fat browning. Irisin, derived from FNDC5, is an exercise-induced myokine that drives brown-fat-like thermogenesis in murine white fat. Here we explored whether cold exposure is an afferent signal for irisin secretion in humans and compared it with FGF21, a brown adipokine in rodents. Cold exposure increased circulating irisin and FGF21. We found an induction of irisin secretion proportional to shivering intensity, in magnitude similar to exercise-stimulated secretion. FNDC5 and/or FGF21 treatment upregulated human adipocyte brown fat gene/protein expression and thermogenesis in a depot-specific manner. These results suggest exercise-induced irisin secretion could have evolved from shivering-related muscle contraction, serving to augment brown fat thermogenesis in concert with FGF21. Irisin-mediated muscle-adipose crosstalk may represent a thermogenic, cold-activated endocrine axis that is exploitable in obesity therapeutics development.

引用

页码：302 / 309

页数：8

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