Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, Taiwan.
Division of Endocrinology, Department of Internal Medicine, Cardinal Tien Hospital, Xindian, Taiwan.
FASEB J. 2020 Feb;34(2):2958-2967. doi: 10.1096/fj.201901925R. Epub 2019 Dec 27.
Fibrinogen-like-protein 1 (FGL1) is a novel hepatokine that plays an important role in hepatic steatosis and insulin resistance. Although FGL1 expression can be detected in adipose tissues, the functions of FGL1 in adipose tissues are still unknown. In this study, 356 participants with (body mass index (BMI) ≥25 kg/m ; n = 134) or without obesity (BMI <25 kg/m ; n = 222) were recruited, and we found that the plasma FGL1 concentrations were significantly higher in obese group than those of in the normal weight group, and were positively correlated with age, BMI, waist circumference, fat content, plasma glucose at 2 hours during an oral glucose tolerance test, and the insulin sensitivity index. In univariate analyses, BMI, waist circumference, total fat, visceral fat, and subcutaneous fat areas were positively correlated with FGL1 levels. After adjusting for age and gender, obesity indices, including the BMI and different fat areas, remained significantly associated with FGL1 levels. In order to investigate the causal relationship between FGL1 and obesity, animal and cell models were used. Overexpression of FGL1 in epididymal adipose tissue by lentiviral vector encoding FGL1 increased the fat pad size, whereas FGL1-knockdown by lentiviral vector encoding short-hairpin RNA targeted to FGL1 decreased high-fat diet-induced adiposity. In addition, 3T3-L1 adipocytes were used to clarify the possible mechanism of FGL1-induced adipogenesis. FGL1 induced adipogenesis through an ERK1/2-C/EBPβ-dependent pathway in 3T3-L1 adipocytes. These findings highlight the pathophysiological role of FGL1 in obesity, and FGL1 might be a novel therapeutic target to combat obesity.
纤维蛋白原样蛋白 1（FGL1）是一种新型的肝分泌物，在肝脂肪变性和胰岛素抵抗中发挥重要作用。尽管在脂肪组织中可以检测到 FGL1 的表达，但 FGL1 在脂肪组织中的功能仍不清楚。在这项研究中，招募了 356 名参与者（体重指数（BMI）≥25kg/m 2；n=134）或无肥胖症（BMI<25kg/m 2；n=222），我们发现肥胖组的血浆 FGL1 浓度明显高于正常体重组，并且与年龄、BMI、腰围、脂肪含量、口服葡萄糖耐量试验 2 小时时的血糖和胰岛素敏感性指数呈正相关。在单变量分析中，BMI、腰围、总脂肪、内脏脂肪和皮下脂肪面积与 FGL1 水平呈正相关。在调整年龄和性别后，肥胖指数，包括 BMI 和不同的脂肪面积，与 FGL1 水平仍呈显著相关。为了研究 FGL1 与肥胖之间的因果关系，使用了动物和细胞模型。通过编码 FGL1 的慢病毒载体在附睾脂肪组织中过表达 FGL1 增加了脂肪垫的大小，而靶向 FGL1 的短发夹 RNA 的慢病毒载体下调 FGL1 则减少了高脂肪饮食诱导的肥胖。此外，还使用了 3T3-L1 脂肪细胞来阐明 FGL1 诱导脂肪生成的可能机制。FGL1 通过 3T3-L1 脂肪细胞中的 ERK1/2-C/EBPβ 依赖性途径诱导脂肪生成。这些发现强调了 FGL1 在肥胖症中的病理生理作用，并且 FGL1 可能是对抗肥胖的新的治疗靶标。
