Dushay Jody, Chui Patricia C, Gopalakrishnan Gosala S, Varela-Rey Marta, Crawley Meghan, Fisher Ffolliott M, Badman Michael K, Martinez-Chantar Maria L, Maratos-Flier Eleftheria
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Gastroenterology. 2010 Aug;139(2):456-63. doi: 10.1053/j.gastro.2010.04.054. Epub 2010 May 5.
BACKGROUND & AIMS: Fibroblast growth factor 21 (FGF21) is an hepatic protein that plays a critical role in metabolism, stimulating fatty acid oxidation in liver and glucose uptake in fat. Systemic administration to obese rodents and diabetic monkeys leads to improved glucose homeostasis and weight loss. In rodents, FGF21 increases with fasting and consumption of a ketogenic diet (KD). In humans, FGF21 correlates with body mass index (BMI), but studies evaluating other parameters show inconsistent results. We examined FGF21 serum levels in lean and obese individuals and in response to dietary manipulation. We also evaluated FGF21 serum levels and liver messenger RNA (mRNA) expression in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).
Serum FGF21 was measured after an overnight fast in individuals with BMI ranging from normal to obese. Volunteers fasted for 16 or 72 hours and then ate a standard meal. Another group consumed KD for 12 days. Serum FGF21 and hepatic mRNA expression were measured in obese individuals with NAFLD or NASH.
There was a positive correlation between BMI and FGF21. There was no change in FGF21 in response to a short fast or KD. A nonstatistically significant fall in FGF21 levels was seen after a 72-hour fast. Hepatic FGF21 mRNA expression was significantly elevated in NAFLD, which correlated with a substantial increase in serum FGF21. In NASH, serum FGF21 but not liver mRNA was increased.
FGF21 correlates with BMI and may be a novel biomarker for NAFLD, but is not nutritionally regulated in humans.
成纤维细胞生长因子21（FGF21）是一种肝脏蛋白，在新陈代谢中起关键作用，可刺激肝脏中的脂肪酸氧化以及脂肪中的葡萄糖摄取。对肥胖啮齿动物和糖尿病猴进行全身给药可改善葡萄糖稳态并减轻体重。在啮齿动物中，FGF21随着禁食和生酮饮食（KD）的摄入而增加。在人类中，FGF21与体重指数（BMI）相关，但评估其他参数的研究结果并不一致。我们检测了瘦人和肥胖个体中FGF21的血清水平以及饮食干预后的反应。我们还评估了非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）患者的FGF21血清水平和肝脏信使核糖核酸（mRNA）表达。
对BMI范围从正常到肥胖的个体进行过夜禁食后测量血清FGF21。志愿者禁食16或72小时，然后进食标准餐。另一组食用KD 12天。测量患有NAFLD或NASH的肥胖个体的血清FGF21和肝脏mRNA表达。
BMI与FGF21之间存在正相关。短期禁食或KD对FGF21无影响。禁食72小时后，FGF21水平有非统计学意义的下降。NAFLD患者肝脏FGF21 mRNA表达显著升高，这与血清FGF21的大幅增加相关。在NASH患者中，血清FGF21升高，但肝脏mRNA未升高。
FGF21与BMI相关，可能是NAFLD的一种新型生物标志物，但在人类中不受营养调节。
