Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
J Hepatol. 2010 Nov;53(5):934-40. doi: 10.1016/j.jhep.2010.05.018. Epub 2010 Jul 17.
BACKGROUND & AIMS: Fibroblast growth factor 21 (FGF21), a hormone primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α (PPARα) activation, has recently been shown to possess beneficial effects on lipid metabolism and hepatic steatosis in animal models. This study investigated the association of FGF21 with nonalcoholic fatty liver disease (NAFLD) in Chinese patients.
Serum FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) in 224 NAFLD and 124 control subjects, and their association with parameters of adiposity, glucose, and lipid profiles and levels of liver injury markers was studied. Besides serum concentrations, the mRNA expression of FGF21 in the liver tissue was also quantified by real-time PCR in 17 subjects with different degrees of steatosis, and was correlated with the levels of intrahepatic lipid. The protein levels of FGF21 were determined by quantitative ELISA.
Serum FGF21 levels in patients with NAFLD (402.38 pg/ml [242.03, 618.25]) were significantly higher than those in control subjects (198.62 pg/ml [134.96, 412.62]) (p<0.01). In human liver tissues, FGF21 mRNA expression increased with the degree of steatosis. Both FGF21 mRNA expression and serum FGF21 concentrations were positively correlated with intrahepatic triglyceride (TG) having r = 0.692 and r = 0.662, respectively, at p<0.01. Furthermore, the increased expression of FGF21 was accompanied by elevated protein levels in liver tissues.
These results support the role of FGF21 as a key regulator of hepatic lipid metabolism in humans, and suggest that serum FGF21 can be potentially used as a biomarker for NAFLD.
成纤维细胞生长因子 21(FGF21)是一种主要由肝脏分泌的激素,它在过氧化物酶体增殖物激活受体-α(PPARα)激活时会对脂质代谢和肝脂肪变性产生有益作用。本研究旨在探讨 FGF21 与中国患者非酒精性脂肪性肝病(NAFLD)之间的关系。
采用酶联免疫吸附试验(ELISA)法检测 224 例 NAFLD 患者和 124 例对照者的血清 FGF21 水平,并研究其与肥胖、血糖和血脂参数及肝损伤标志物水平的相关性。除血清浓度外,还通过实时 PCR 定量检测了 17 例不同程度脂肪变性患者肝组织中 FGF21 的 mRNA 表达,并与肝内脂质水平相关。采用定量 ELISA 法检测 FGF21 蛋白水平。
NAFLD 患者血清 FGF21 水平(402.38 pg/ml[242.03,618.25])明显高于对照组(198.62 pg/ml[134.96,412.62])(p<0.01)。在人类肝组织中,FGF21 mRNA 表达随着脂肪变性程度的增加而增加。FGF21 mRNA 表达和血清 FGF21 浓度均与肝内三酰甘油(TG)呈正相关,相关系数分别为 r = 0.692 和 r = 0.662,均 p<0.01。此外,FGF21 的表达增加伴随着肝组织中蛋白水平的升高。
这些结果支持 FGF21 作为人类肝脏脂质代谢关键调节因子的作用,并提示血清 FGF21 可作为 NAFLD 的潜在生物标志物。