Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding.
Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding.
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循环的FGF21是肝脏的，并在进食和过度喂养过程中增强了葡萄糖的摄取。
DOI：
10.2337/db14-0595
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发表时间：
2014-12
期刊：
影响因子：
7.7
通讯作者：
Potthoff MJ
中科院分区：
文献类型：
--
作者：
Markan KR;Naber MC;Ameka MK;Anderegg MD;Mangelsdorf DJ;Kliewer SA;Mohammadi M;Potthoff MJ
成纤维细胞生长因子（FGF）21是一种内分泌激素，在多种组织中表达，在生理上起维持能量稳态的作用。FGF21由于其对改善胰岛素敏感性的快速和有效作用而被追求作为糖尿病和肥胖症的治疗靶点。然而，FGF 21是否在生理条件下增强胰岛素敏感性仍不清楚。在这里，我们发现肝脏来源的FGF21在禁食期间进入循环，但在再喂养的早期阶段仍然存在并发挥作用。在长时间禁食后，FGF 21作为胰岛素增敏剂来克服由禁食诱导的外周胰岛素抵抗，从而使葡萄糖摄取最大化。同样，FGF21在过度喂养期间从肝脏产生，并减轻外周胰岛素抵抗。DIO FGF21肝脏特异性敲除小鼠，而非FGF21脂肪特异性敲除小鼠，胰岛素抵抗增加，棕色脂肪组织介导的葡萄糖处置减少。这些数据与FGF 21在急性再喂养和过度喂养条件下生理上作为胰岛素增敏剂起作用的概念一致。
Fibroblast growth factor (FGF)21 is an endocrine hormone that is expressed in multiple tissues and functions physiologically to maintain energy homeostasis. FGF21 is being pursued as a therapeutic target for diabetes and obesity because of its rapid and potent effects on improving insulin sensitivity. However, whether FGF21 enhances insulin sensitivity under physiologic conditions remains unclear. Here, we show that liver-derived FGF21 enters the circulation during fasting but also remains present and functional during the early stage of refeeding. After a prolonged fast, FGF21 acts as an insulin sensitizer to overcome the peripheral insulin resistance induced by fasting, thereby maximizing glucose uptake. Likewise, FGF21 is produced from the liver during overfeeding and mitigates peripheral insulin resistance. DIO FGF21 liver-specific knockout, but not FGF21 adipose-specific knockout, mice have increased insulin resistance and decreased brown adipose tissue–mediated glucose disposal. These data are compatible with the concept that FGF21 functions physiologically as an insulin sensitizer under conditions of acute refeeding and overfeeding.
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影响因子：
4.8
作者：
Fujii, N;Hirshman, MF;Goodyear, LJ
通讯作者：
Goodyear, LJ
影响因子：
4.1
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FERRE, P;LETURQUE, A;GIRARD, J
通讯作者：
GIRARD, J
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29
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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
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Scherer PE
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29
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Eguchi J;Wang X;Yu S;Kershaw EE;Chiu PC;Dushay J;Estall JL;Klein U;Maratos-Flier E;Rosen ED
通讯作者：
Rosen ED
影响因子：
4.8
作者：
Kurosu, Hiroshi;Choi, Mihwa;Kuro-o, Makoto
通讯作者：
Kuro-o, Makoto