Insulin and Incretin Biology, Hagedorn Research Institute, Novo Nordisk A/S, Gentofte, Denmark.
Clin Endocrinol (Oxf). 2011 Oct;75(4):514-9. doi: 10.1111/j.1365-2265.2011.04084.x.
Fibroblast growth factor (FGF21) is a potent regulator of glucose and lipid metabolism. In rodents, the hepatic expression of FGF21 is controlled by fasting and a circadian regulation, but the physiological role and regulation of FGF21 in humans is not well established. Therefore, the objective of this study was to elucidate the 24-h profiling of plasma FGF21 during a 72-h fast.
After an initial 12-h overnight fast, plasma levels of FGF21 together with circulating levels of glucose, insulin, glucagon and free fatty acids (FFA) were measured every 6 h during a 72-h fast in healthy female volunteers (n = 14).
During the fast, plasma glucose and serum insulin gradually decreased whilst glucagon and FFA levels increased. Mean 24-h plasma FGF21 levels did not increase during the 72-h fast, but, despite large inter-individually variations, a significant circadian rhythm was observed. Thus, during the first day, plasma FGF21 increased from 125 pg/ml (16-142) at 8.30 a.m to peak levels of 224 pg/ml (88-326) at 2.30 a.m (P = 0·0215), the second day from 60 pg/ml (7-74) at 8.30 a.m to 268 pg/ml (103-410) at 2.30 a.m. (P = 0·0010) and the third day from 94 pg/ml (9-146) to 151 pg/ml (87-207) at 2.30 a.m. (P = 0·0049). Cortisol also showed circadian regulation and peaked at 8.30 a.m every day, 6 h after the observed FGF21 peak.
Plasma FGF21 follows a circadian rhythm during a 72-h fast in healthy female subjects. The circadian regulation has a stronger impact on plasma FGF21 than the fasting status over 72-h period.
成纤维细胞生长因子 21（FGF21）是一种调节葡萄糖和脂质代谢的有效物质。在啮齿动物中，FGF21 的肝脏表达受禁食和昼夜节律调节控制，但 FGF21 在人体中的生理作用和调节尚未得到很好的确定。因此，本研究的目的是阐明在 72 小时禁食期间，血浆 FGF21 的 24 小时变化情况。
在初始的 12 小时夜间禁食后，在 72 小时禁食期间，每隔 6 小时测量健康女性志愿者（n=14）的血浆 FGF21 水平以及循环血糖、胰岛素、胰高血糖素和游离脂肪酸（FFA）水平。
在禁食期间，血浆葡萄糖和血清胰岛素逐渐下降，而胰高血糖素和 FFA 水平升高。尽管个体间存在很大差异，但在 72 小时禁食期间，平均 24 小时血浆 FGF21 水平并未增加，但仍观察到明显的昼夜节律。因此，在第一天，血浆 FGF21 从上午 8:30 的 125pg/ml（16-142）增加到凌晨 2:30 的峰值 224pg/ml（88-326）（P=0.0215），在第二天从上午 8:30 的 60pg/ml（7-74）增加到凌晨 2:30 的 268pg/ml（103-410）（P=0.0010），在第三天从上午 8:30 的 94pg/ml（9-146）增加到凌晨 2:30 的 151pg/ml（87-207）（P=0.0049）。皮质醇也呈现昼夜节律调节，每天上午 8:30 达到峰值，比观察到的 FGF21 峰值早 6 小时。
在健康女性受试者的 72 小时禁食期间，血浆 FGF21 遵循昼夜节律。在 72 小时期间，昼夜节律对血浆 FGF21 的影响比禁食状态更强。
