Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease.
Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease.
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DOI：
10.1053/j.gastro.2010.04.054
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发表时间：
2010-08
期刊：
影响因子：
29.4
通讯作者：
Maratos-Flier E
中科院分区：
文献类型：
--
作者：
Dushay J;Chui PC;Gopalakrishnan GS;Varela-Rey M;Crawley M;Fisher FM;Badman MK;Martinez-Chantar ML;Maratos-Flier E
成纤维细胞生长因子21（FGF21）是一种肝脏蛋白，其在代谢中起关键作用，刺激肝脏中的脂肪酸氧化和脂肪中的葡萄糖摄取。对肥胖啮齿动物和糖尿病猴的全身给药导致葡萄糖稳态改善和体重减轻。在啮齿类动物中，FGF21随着禁食和生酮饮食（KD）的消耗而增加。在人类中，FGF 21与体重指数相关，但评估其他参数的研究显示不一致的结果。我们研究了瘦和肥胖个体的FGF21血清水平以及对饮食操作的反应。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）的FGF21血清水平和肝脏mRNA表达。在BMI范围从正常到肥胖的个体中过夜禁食后测量血清FGF21。志愿者禁食16或72小时，然后吃标准餐。另一组服用KD 12天。在患有NAFLD或NASH的肥胖个体中测量血清FGF21和肝脏mRNA表达。BMI与FGF21呈正相关。FGF21对短禁食或KD的反应没有变化。在禁食72小时后观察到FGF 21水平的非统计学显著下降。肝脏FGF21 mRNA表达在NAFLD中显著升高，这与血清FGF21的显著增加相关。在NASH中，血清FGF21而非肝脏mRNA增加。FGF21与BMI相关，可能是NAFLD的新生物标志物，但在人类中不受营养调节。
Fibroblast growth factor 21 (FGF21) is a 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, 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 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 non-statistically 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.