Global Research, Novo Nordisk A/S, Måløv, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
J Endocrinol. 2018 Oct 1;239(1):73–80. doi: 10.1530/JOE-18-0002.
Fibroblast growth factor 21 (FGF21) is a metabolic regulator of energy and lipid metabolism. FGF21 is highly expressed in liver while FGF21 receptors (beta-klotho (KLB) and FGFR1c) are highly expressed in white adipose tissues (WATs). Plasma FGF21 has been shown to be increased after 7–10 days of fasting but oppositely plasma FGF21 is also increased in obesity. The aim of this study was to measure the effect of 60 h of fasting on plasma FGF21 levels in obese and lean subjects and to determine the gene expression of KLB and FGFR1c in the subcutaneous WAT before, during and after 60 h of fasting. Eight obese (BMI >30 kg/m2) and seven lean subjects (BMI <25 kg/m2) were fasted for 60 h and blood samples were taken at time 0 and after 12, 36 and 60 h of fasting. A biopsy from the subcutaneous WAT was taken at time 0, 12 and 60 h of fasting. FGF21 was measured in plasma by an ELISA and mRNA expression of KLB and FGFR1c was measured in WAT by quantitative PCR (qPCR). The fast significantly decreased plasma FGF21 in obese subjects while no change in plasma FGF21 was observed in lean subjects. Interestingly, KLB was significantly decreased in WAT in response to fasting in both lean and obese subjects indicating a potential important adaptive regulation of KLB in response to fasting.
成纤维细胞生长因子 21（FGF21）是能量和脂质代谢的代谢调节剂。FGF21 在肝脏中高度表达，而 FGF21 受体（β-klotho（KLB）和 FGFR1c）在白色脂肪组织（WAT）中高度表达。已经表明，禁食 7-10 天后血浆 FGF21 增加，但肥胖症患者的血浆 FGF21 也增加。本研究的目的是测量 60 小时禁食对肥胖和瘦受试者血浆 FGF21 水平的影响，并确定在 60 小时禁食之前、期间和之后皮下 WAT 中 KLB 和 FGFR1c 的基因表达。8 名肥胖（BMI>30kg/m2）和 7 名瘦受试者（BMI<25kg/m2）禁食 60 小时，并在禁食 0、12、36 和 60 小时时采集血样。在禁食 0、12 和 60 小时时从皮下 WAT 中取活检。通过 ELISA 测量血浆中的 FGF21，并通过定量 PCR（qPCR）测量 WAT 中 KLB 和 FGFR1c 的 mRNA 表达。禁食显著降低了肥胖受试者的血浆 FGF21，而瘦受试者的血浆 FGF21 没有变化。有趣的是，KLB 在瘦和肥胖受试者的 WAT 中均因禁食而显著降低，表明 KLB 在禁食时可能发生重要的适应性调节。
