JCEM：FGE–21浓度与肝脏脂肪含量相关

成纤维细胞生长因子（FGF）–21在肝脏中高度表达，并在啮齿动物中调节葡萄糖和脂质代谢。目前主要在成年人肥胖和脂肪肝对循环FGF–21水平的影响。因此，为了在消瘦和伴有低和高肝脏脂肪含量（分别为HFF%<5.5 %和HFF%≥5.5 %）的肥胖青少年测量血浆FGF–21水平，探讨血浆FGF–21水平与肝脏脂肪含量、肝细胞凋亡数量和胰岛素敏感性的关系，来自美国耶鲁大学医学院的Sonia Caprio教授及其团队进行了一项研究，该研究发现在肥胖青少年，FGF–21浓度与肝脏脂肪含量和肝细胞凋亡标记物呈显著独立相关。该研究结果在线发表在2013年4月26日的美国《临床内分泌代谢杂志》（The Journal of Clinical Endocrinology & Metabolism）上。

该研究中，共有217例消瘦和伴有低和高HFF%的肥胖青少年（消瘦31例，肥胖低HFF%107例，肥胖高HFF%79例）进行口服葡萄糖耐量试验（OGTT），快速梯度磁共振成像测量HFF%和腹部脂肪分布。测量细胞角蛋白18水平（CK18）作为肝细胞凋亡的生物标志物。在一个青少年亚组进行两步法高胰岛素正常葡萄糖钳夹试验和肝活检（14例），分别评估胰岛素敏感性和脂肪肝。

该研究结果表明，与对照组相比，肥胖青少年有更高的FGF–21水平，特别是在那些伴有高HFF的青少年（P＜0.001）。FGF–21与肥胖指数（P＜0.001）、内脏脂肪（r²=0.240，P＜0.001）、肝脏脂肪含量（r²=0.278，P＜0.001）、CK18（r²=0.217，P＜0.001）和丙氨酸氨基转移酶（r²=0.164，P＜0.001）显著相关。在伴有脂肪肝的受试者，FGF–21水平与非酒精性脂肪性肝病活动度（NAS）积分（r²=0.27，P＜0.04）显著相关。逐步回归分析显示这些相关性独立于体重指数、内脏脂肪和胰岛素敏感性。曾记录到FGF–21与胰岛素抵抗指数、肝脏抵抗指数和脂肪抵抗指数呈负相关，然而，在校正肝脏脂肪含量后，这种相关性消失。

该研究发现，在肥胖青少年，特别是在那些伴有脂肪肝的青少年，血浆PGF–21水平增加。在肥胖青少年，FGF–21浓度与肝脏脂肪含量和肝细胞凋亡标记物呈显著独立相关。

与肝脏相关的拓展阅读：

• ACC2013：绝经增加肝脏脂肪变性风险
• Cell:肝脏发育研究获进展
• Diabetes：郭非凡等揭示下丘脑ATF4调控肝脏胰岛素敏感性的新功能
• Hepatology：肝脏转化生长因子β可诱发肝癌起始细胞并促进肝癌发生
• J Biol Chem：研究发现HCV损害肝脏的线索
• BJGP:的“红绿灯”试验用于肝脏疾病的早期诊断
更多信息请点击：有关肝脏更多资讯

Circulating levels of FGF-21 in obese youth: associations with liver fat content and markers of liver damage.
Objective
Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates glucose and lipid metabolism in rodents. The effects of obesity and fatty liver on circulating FGF-21 levels have been described mainly in adults. Herein, we measured plasma FGF-21 levels in lean and obese adolescents with low and high hepatic fat content (HFF%<5.5 % and HFF%≥5.5 %, respectively) and explored their relationship with hepatic fat content, measures of hepatic apoptosis and insulin sensitivity.
Methods
A total of 217 lean and obese adolescents with both low and high HFF% (Lean=31; Obese low HFF%=107; and obese high HFF%=79) underwent an Oral Glucose Tolerance Test (OGTT), a fast gradient Magnetic Resonance Imaging to measure the %HFF and abdominal fat distribution. Cytokeratin 18 levels (CK18) were measured as biomarker of liver apoptosis. A subset of adolescents underwent a two-step hyperinsulinemic-euglycemic clamp, and a liver biopsy (N=14), to assess insulin sensitivity and steatohepatitis, respectively.
Results
Compared to controls, FGF-21 levels were higher in obese youth, especially in those with high HFF (p<0.001). FGF-21 significantly correlated with adiposity indexes (P<0.001), Visceral Fat (r2=0.240, P<0.001), hepatic fat content (r2=0.278, P<0.001), CK18 (r2=0.217, P<0.001) and Alanine Aminotransferase (r2=0.164, P<0.001). In subjects with steatoheaptitis, FGF-21 levels significantly correlated with the non-alcoholic fatty liver disease activity (NAS) score (r2=0.27, P=0.04). Stepwise regression analysis indicated that these relationships are independent of Body Mass Index, visceral fat and insulin sensitivity. An inverse correlation was documented with insulin, hepatic and adipose resistance indexes which disappeared after adjusting for hepatic fat content.
Conclusions
Plasma FGF-21 levels are increased in obese adolescents, particularly in those with fatty liver. FGF-21 concentrations significantly and independently correlate with hepatic fat content and markers of hepatic apoptosis in obese youths.