The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARα activation in man
The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARα activation in man
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DOI：
10.1016/j.cmet.2008.06.014
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发表时间：
2008-08-06
期刊：
影响因子：
29
通讯作者：
Rudling, Mats
中科院分区：
文献类型：
--
作者：
Gaelman, Cecilia;Lundasen, Tomas;Rudling, Mats
FGF21是一种关键的代谢调节剂，对啮齿动物的禁食适应至关重要，并由PPAR α直接调节。然而，FGF21在人类中的生理作用尚未明确，我们的研究也对其进行了研究。在76名健康个体中，血清FGF21变化了250倍，与年龄、性别、体重指数（BMI）、血脂或血糖无关。FGF21水平无日变化，与胆汁酸或胆固醇合成无关。禁食2周或饲喂生酮饮食（KD）诱导的酮症不影响FGF21水平，而禁食7天后FGF21水平升高74%。高甘油三酯血症非糖尿病患者FGF21水平升高2倍，非诺贝特治疗期间FGF21水平进一步升高28%。FGF21在人血浆中循环，并通过极端禁食和PPAR α激活而增加。广泛的个体间差异和独立于FGF21水平的生酮诱导表明，FGF21在人类中的生理作用可能与在小鼠中的不同。
FGF21 is a critical metabolic regulator, pivotal for fasting adaptation and directly regulated by PPAR alpha in rodents. However, the physiological role of FGF21 in man is not yet defined and was investigated in our study. Serum FGF21 varied 250-fold among 76 healthy individuals and did not relate to age, gender, body mass index (BMI), serum lipids, or plasma glucose. FGF21 levels had no diurnal variation and were unrelated to bile acid or cholesterol synthesis. Ketosis induced by a 2 (Jay fast or feeding a ketogenic diet (KD) did not influence FGF21 levels, whereas a 74% increase occurred after 7 days of fasting. Hypertriglyceridemic nondiabetic patients had 2-fold elevated FGF21 levels, which were further increased by 28% during fenofibrate treatment. FGF21 circulates in human plasma and increases by extreme fasting and PPAR alpha activation. The wide interindividual variation and the induction of ketogenesis independent of FGF21 levels indicate that the, physiological role of FGF21 in humans may differ from that in mice.