Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans.
Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans.
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DOI：
10.1016/j.cmet.2013.12.017
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发表时间：
2014-02-04
期刊：
影响因子：
29
通讯作者：
Celi FS
中科院分区：
文献类型：
--
作者：
Lee P;Linderman JD;Smith S;Brychta RJ;Wang J;Idelson C;Perron RM;Werner CD;Phan GQ;Kammula US;Kebebew E;Pacak K;Chen KY;Celi FS
人类冷激活棕色脂肪组织（BAT）的重新发现，提高了对识别BAT激活剂代谢益处的研究兴趣。特别令人感兴趣的是能够使脂肪变褐的细胞因子。鸢尾素来源于FNDC5，是一种运动诱导的肌因子，在小鼠白色脂肪中驱动棕色脂肪样的产热。在这里，我们探讨了寒冷暴露是否是人类鸢尾素分泌的传入信号，并将其与啮齿类动物中的棕色脂肪因子FGF21进行了比较。低温暴露增加了循环鸢尾素和FGF21。我们发现鸢尾素的分泌与颤抖强度成正比，其程度与运动刺激分泌相似。FNDC5和/或FGF21处理上调了人脂肪细胞棕色脂肪基因/蛋白的表达和产热，并以储存特异性的方式进行。这些结果表明，运动诱导的鸢尾素分泌可能是从与颤抖相关的肌肉收缩进化而来的，与FGF21一起增加棕色脂肪的产热作用。鸢尾素介导的肌肉-脂肪串扰可能代表了一种产热、冷激活的内分泌轴，可用于肥胖治疗的开发。
Rediscovery of cold-activated brown adipose tissue (BAT) in humans has boosted research interest into 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 up-regulated 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, exploitable in obesity therapeutics development.
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影响因子：
7.7
作者：
Saito M;Okamatsu-Ogura Y;Matsushita M;Watanabe K;Yoneshiro T;Nio-Kobayashi J;Iwanaga T;Miyagawa M;Kameya T;Nakada K;Kawai Y;Tsujisaki M
通讯作者：
Tsujisaki M
影响因子：
5.8
作者：
Chen, Kong Y.;Brychta, Robert J.;Celi, Francesco S.
通讯作者：
Celi, Francesco S.
影响因子：
5.7
作者：
Chartoumpekis, Dionysios V.;Habeos, Ioannis G.;Papavassiliou, Athanasios G.
通讯作者：
Papavassiliou, Athanasios G.
影响因子：
3.7
作者：
Roca-Rivada A;Castelao C;Senin LL;Landrove MO;Baltar J;Belén Crujeiras A;Seoane LM;Casanueva FF;Pardo M
通讯作者：
Pardo M
影响因子：
3.7
作者：
Raschke S;Elsen M;Gassenhuber H;Sommerfeld M;Schwahn U;Brockmann B;Jung R;Wisløff U;Tjønna AE;Raastad T;Hallén J;Norheim F;Drevon CA;Romacho T;Eckardt K;Eckel J
通讯作者：
Eckel J