FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms.
FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms.
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DOI：
10.1016/j.cmet.2017.03.005
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发表时间：
2017-04-04
期刊：
影响因子：
29
通讯作者：
Potthoff MJ
中科院分区：
文献类型：
--
作者：
BonDurant LD;Ameka M;Naber MC;Markan KR;Idiga SO;Acevedo MR;Walsh SA;Ornitz DM;Potthoff MJ
FGF21是一种调节能量稳态和胰岛素敏感性的内分泌激素。FGF 21的作用机制和负责这些作用的组织一直存在争议，脂肪组织和中枢神经系统都被确定为介导胰岛素敏感性、能量消耗和体重减轻的FGF 21依赖性增加的靶位点。在这里，我们表明，虽然FGF21的急性胰岛素增敏作用需要FGF21向脂肪组织的信号传导，但FGF21向脂肪组织的信号传导并不需要其增加能量消耗和降低体重的慢性作用。此外，与以前的研究相比，我们发现脂联素与FGF 21在增加胰岛素敏感性和能量消耗方面的代谢作用无关。相反，FGF21通过对棕色脂肪组织的作用而急剧增强胰岛素敏感性。我们的数据表明，FGF 21的急性和慢性作用可以通过脂肪依赖性和非依赖性机制来分离。FGF21的药理学施用增加胰岛素敏感性并促进体重减轻。邦杜朗等人表明，FGF 21向脂肪组织的信号传导对于FGF 21的急性胰岛素增敏作用是必需的，但不是其对体重的作用。重要的是，特定于棕色脂肪细胞的FGF21信号传导的丧失破坏了FGF21介导的葡萄糖处置。
FGF21 is an endocrine hormone that regulates energy homeostasis and insulin sensitivity. The mechanism of FGF21 action and the tissues responsible for these effects have been controversial, with both adipose tissues and the central nervous system being identified as the target site mediating FGF21-dependent increases in insulin sensitivity, energy expenditure, and weight loss. Here we show that while FGF21 signaling to adipose tissue is required for the acute insulin sensitizing effects of FGF21, FGF21 signaling to adipose tissue is not required for its chronic effects to increase energy expenditure and lower body weight. Also, in contrast to previous studies, we found that adiponectin is dispensable for the metabolic effects of FGF21 in increasing insulin sensitivity and energy expenditure. Instead, FGF21 acutely enhances insulin sensitivity through actions on brown adipose tissue. Our data reveal that the acute and chronic effects of FGF21 can be dissociated through adipose-dependent and -independent mechanisms. Pharmacological administration of FGF21 increases insulin sensitivity and promotes weight loss. BonDurant et al. show that FGF21 signaling to adipose tissues is essential for the acute insulin-sensitizing effects of FGF21, but not its effects on body weight. Importantly, loss of FGF21 signaling specifically to brown adipocytes disrupts FGF21-mediated glucose disposal.