Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis.
Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis.
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成纤维细胞生长因子 21 缺乏会减弱实验性结肠炎诱导的脂肪组织脂解作用
DOI：
10.1155/2017/3089378
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发表时间：
2017
影响因子：
2
通讯作者：
Feng W
中科院分区：
文献类型：
--
作者：
Liu L;Zhao C;Yang Y;Kong X;Shao T;Ren L;Zhuang X;Yin B;Dryden G;McClain C;Luan W;Feng W
目的炎症性肠病（IBD）患者营养缺乏是常见的。脂肪组织在调节能量平衡中起着至关重要的作用。成纤维细胞生长因子21（FGF 21）是一种重要的内分泌代谢调节因子，在脂质体内平衡中发挥着重要作用。我们研究了FGF 21在实验性结肠炎诱导的附睾白色脂肪组织（eWAT）脂解中的影响。方法采用2.5%葡聚糖硫酸钠（DSS）诱导小鼠结肠炎模型。使用抗体中和或敲除（KO）小鼠研究FGF 21的作用。测定脂肪分解指数和脂肪分解酶。此外，用IL-6预处理3T3-L1细胞，然后用重组人FGF21（rhFGF21）处理;评估脂解。结果DSS能显著降低大鼠eWAT/体重比值，升高血清游离脂肪酸（FFA）和甘油浓度，提示DSS能促进脂肪组织脂解。eWAT细胞内脂解酶表达/活化显著增加。这些变化在FGF21 KO小鼠中以及通过循环FGF21中和而显着减弱。此外，DSS治疗显著增加血清IL-6和FGF 21水平。IL-6预处理是FGF 21刺激3T3-L1细胞脂肪分解的必要条件。结论实验性结肠炎通过IL-6/FGF21介导的信号通路诱导eWAT脂解。
Aims Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD). Adipose tissue plays a critical role in regulating energy balance. Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator with emerging beneficial roles in lipid homeostasis. We investigated the impact of FGF21 in experimental colitis-induced epididymal white adipose tissue (eWAT) lipolysis. Methods Mice were given 2.5% dextran sulfate sodium (DSS) ad libitum for 7 days to induce colitis. The role of FGF21 was investigated using antibody neutralization or knockout (KO) mice. Lipolysis index and adipose lipolytic enzymes were determined. In addition, 3T3-L1 cells were pretreated with IL-6, followed by recombinant human FGF21 (rhFGF21) treatment; lipolysis was assessed. Results DSS markedly decreased eWAT/body weight ratio and increased serum concentrations of free fatty acid (FFA) and glycerol, indicating increased adipose tissue lipolysis. eWAT intracellular lipolytic enzyme expression/activation was significantly increased. These alterations were significantly attenuated in FGF21 KO mice and by circulating FGF21 neutralization. Moreover, DSS treatment markedly increased serum IL-6 and FGF21 levels. IL-6 pretreatment was necessary for the stimulatory effect of FGF21 on adipose lipolysis in 3T3-L1 cells. Conclusions Our results demonstrate that experimental colitis induces eWAT lipolysis via an IL-6/FGF21-mediated signaling pathway.