An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice.
An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice.
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DOI：
10.1016/j.cmet.2013.03.019
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发表时间：
2013-05-07
期刊：
影响因子：
29
通讯作者：
Scherer PE
中科院分区：
文献类型：
--
作者：
Holland WL;Adams AC;Brozinick JT;Bui HH;Miyauchi Y;Kusminski CM;Bauer SM;Wade M;Singhal E;Cheng CC;Volk K;Kuo MS;Gordillo R;Kharitonenkov A;Scherer PE
FGF 21是成纤维细胞生长因子（FGF）超家族的成员之一，近年来成为一种新的代谢和能量利用调节因子。然而，FGF 21介导其作用的确切机制尚未阐明。有大量证据表明，胰岛素抵抗可能是由于脂毒性引起的胰岛素反应组织中细胞内脂质的异常积累而引起的。特别是鞘脂神经酰胺已涉及该过程。在这里，我们表明，FGF 21迅速和强大的刺激脂联素分泌啮齿动物，同时减少积累的神经酰胺在肥胖动物。重要的是，脂联素基因敲除小鼠对FGF 21给药引起的能量消耗和神经酰胺降低效应的变化不敏感。此外，FGF 21仅在脂联素功能性存在时降低糖尿病Lepob/ob小鼠和饮食诱导的肥胖（DIO）小鼠的血糖水平并增强胰岛素敏感性。总的来说，这些数据表明FGF 21是脂联素分泌的有效调节剂，并且FGF 21关键地依赖于脂联素来发挥其血糖和胰岛素增敏作用。
FGF21, a member of the fibroblast growth factor (FGF) superfamily has recently emerged as a novel regulator of metabolism and energy utilization. However, the exact mechanism(s) whereby FGF21 mediates its actions have not been elucidated. There is considerable evidence that insulin resistance may arise from aberrant accumulation of intracellular lipids in insulin responsive tissues due to lipotoxicity. In particular the sphingolipid ceramide has been implicated in this process. Here, we show that FGF21 rapidly and robustly stimulates adiponectin secretion in rodents, while diminishing accumulation of ceramides in obese animals. Importantly, adiponectin knockout mice are refractory to changes in energy expenditure and ceramide-lowering effects evoked by FGF21 administration. Moreover, FGF21 lowers blood glucose levels and enhances insulin sensitivity in diabetic Lepob/ob mice and diet-induced obese (DIO) mice, only when adiponectin is functionally present. Collectively, these data suggest that FGF21 is a potent regulator of adiponectin secretion, and that FGF21 critically depends on adiponectin to exert its glycemic and insulin sensitizing effects.
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影响因子：
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作者：
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通讯作者：
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通讯作者：
Elmquist JK
影响因子：
15.9
作者：
Combs, TP;Berg, AH;Rossetti, L
通讯作者：
Rossetti, L