FGF-21  成纤维细胞生长因子-21是一个脂肪和肝脏源性激素调节脂肪酸代谢、能量代谢、 改善胰岛素抵抗和瘦素抵抗现象、 保护酒精性肝脏损伤、纠正肥胖性脂肪肝。

FGF-21 是一个肝脏和脂肪细胞合成和分泌的生长因子和脂肪因子， 具有非常重要作用的生物学作用和药物学作用。FGF21可以保护胰腺的贝塔细胞，.促进胰岛素的分泌，保护糖尿病动物的血糖稳态。FGF-21对酒精性肝脏损伤和肥胖性脂肪肝都有显著的保护作用。它可以促进脂肪利用和燃烧， 抑制脂肪合成改进细胞的能量代谢功能，抑制肝脏纤维化进程。FGF-21 可以纠正肥胖对肝脏的影响。肥胖患者血清FGF-21含量升高。神经性厌食症患者血清FGF-21含量降低。研究资料表明， 糖尿病患者血清FGF-21 成纤维细胞生长因子-21(FGF-21)是FGFs家族的一个新成员.虽然FGF-21表现出与胰岛素类似的糖脂代谢调节作用,并受葡萄糖转运蛋白1(GLUT1)和胰高血糖素调节,但并不导致低血糖,因此有望成为治疗糖尿病的新药。

北京爱迪博生物是国际上最早开展FGF-21应用性研究的少数几个高科技公司。爱迪博生物开发的人和小鼠重组FGF-21 活性蛋白、单克隆抗体、 多克隆抗体最早出口到美国和欧洲市场，目前国际所流行使用FGF-21产品多是北京爱迪博生物开发的产品。爱迪博生物开发的人活性FGF-21酶联试剂盒， 具有特异性高的特点，因为使用双抗体捕获技术，不识别血清或血浆中FGF-21降解多肽片段， 她是真正的活性型FGF-21免疫定量试剂盒。它可以准确反映内源性活性FGF-21含量的变化。目前市场流行的FGF-21竞争性试剂盒特异性不高，不能识别人和小鼠序列的差异，不能准确定量活性FGF-21。另外一种FGF-21试剂盒因为所用的双抗体抗原决定簇特异性不高，人血清样本检测离散度非常大，研究结果的统计学处理后差异性大到难以接受，检测糖尿病、肥胖和空腹的结果偏差很大，可信度证据不足。

Molecular analysis of zebrafish Fgf21. (A) Phylogenetic tree comparing zebrafish Fgf21 (zFgf21) with human FGFs (hFGFs).

Fibroblast growth factor 21 corrects obesity in mice

Fibroblast growth factor 21 (FGF21) is a metabolic regulator that provides efficient and durable glycemic and lipid control in various animal models. However, its potential to treat obesity, a major health concern affecting over 30% of the population, has not been fully explored. Here we report that systemic administration of FGF21 for 2 wk in diet-induced obese and ob/ob mice lowered their mean body weight by 20% predominantly via a reduction in adiposity. Although no decrease in total caloric intake or effect on physical activity was observed, FGF21-treated animals exhibited increased energy expenditure, fat utilization, and lipid excretion, reduced hepatosteatosis, and ameliorated glycemia. Transcriptional and blood cytokine profiling studies revealed effects consistent with the ability of FGF21 to ameliorate insulin and leptin resistance, enhance fat oxidation and suppress de novo lipogenesis in liver as well as to activate futile cycling in adipose. Overall, these data suggest that FGF21 exhibits the therapeutic characteristics necessary for an effective treatment of obesity and fatty liver disease and provides novel insights into the metabolic determinants of these activities.

Coskun T, et al. Endocrinology. 2008 Dec;149(12):6018-27. Epub 2008 Aug 7.

FGF21 Reverses Hepatic Steatosis, Increases Energy Expenditure and Improves Insulin Sensitivity in Diet-induced Obese Mice

OBJECTIVES- Fibroblast growth factor 21 (FGF21) has emerged as an important metabolic regulator of glucose and lipid metabolism. The aims of the current study are to evaluate the role of FGF21 in energy metabolism and to provide mechanistic insights into its glucose and lipid-lowering effects in a high fat diet-induced obesity (DIO) model. RESEARCH DESIGN AND METHODS- DIO or normal lean mice were treated with vehicle or recombinant murine FGF21. Metabolic parameters including body weight, glucose and lipid levels were monitored, and hepatic gene expression was analyzed. Energy metabolism and insulin sensitivity were assessed using indirect calorimetry and hyperinsulinemic-euglycemic clamp techniques. RESULTS- FGF21 dose-dependently reduced body weight and whole body fat mass in DIO mice owing to marked increases in total energy expenditure and physical activity levels. FGF21 also reduced blood glucose, insulin, and lipid levels and reversed hepatic steatosis. The profound reduction of hepatic triglyceride levels was associated with FGF21 inhibition of nuclear SREBP-1 and the expression of a wide array of genes involved in fatty acid and triglyceride synthesis. FGF21 also dramatically improved hepatic and peripheral insulin sensitivity in both lean and DIO mice independently of reduction in body weight and adiposity. CONCLUSIONS- FGF21 corrects multiple metabolic disorders in DIO mice and has the potential to become a powerful therapeutic to treat hepatic steatosis, obesity and type 2 diabetes.

Xu J, et al. Diabetes. 2008 Oct 7. [Epub ahead of print]

FGF21 attenuates lipolysis in human adipocytes - a possible link to improved insulin sensitivity

Fibroblast growth factor 21 (FGF21) is active in murine adipocytes and has beneficial metabolic effects in animal models of type 2 diabetes mellitus. We assessed whether FGF21 influences lipolysis in human adipocytes and 3T3-L1 cells. FGF21 had no short-time effect (h) while a 3-day incubation with FGF21 attenuated hormone-stimulated lipolysis. FGF21 did not influence the mRNA expression of genes involved in regulating lipolysis, but significantly reduced the expression of the lipid droplet-associated phosphoprotein perilipin without affecting differentiation. Via reduced release of fatty acids into the circulation, the anti-lipolytic effect could be a mechanism through which FGF21 promotes insulin sensitivity in man.

Arner P, et al. FEBS Lett. 2008 May 28;582(12):1725-30. Epub 2008 May 5.