成纤维细胞生长因子21缺乏减轻实验性结肠炎诱导的脂肪组织脂解作用。
Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis.
作者信息
Liu Liming, Zhao Cuiqing, Yang Ying, Kong Xiaoxia, Shao Tuo, Ren Li, Zhuang Xinyu, Yin Baishuang, Dryden Gerald, McClain Craig, Luan Weimin, Feng Wenke
机构信息
College of Animal Science and Technology, Key Laboratory of Animal Production and Production Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin 130118, China.
Departments of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
出版信息
Gastroenterol Res Pract. 2017;2017:3089378. doi: 10.1155/2017/3089378. Epub 2017 May 11.
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.
目的
营养缺乏在炎症性肠病（IBD）患者中很常见。脂肪组织在调节能量平衡中起关键作用。成纤维细胞生长因子21（FGF21）是一种重要的内分泌代谢调节因子，在脂质稳态中发挥着新出现的有益作用。我们研究了FGF21对实验性结肠炎诱导的附睾白色脂肪组织（eWAT）脂解的影响。
方法
给小鼠自由饮用2.5%的葡聚糖硫酸钠（DSS）7天以诱导结肠炎。使用抗体中和或基因敲除（KO）小鼠研究FGF21的作用。测定脂解指数和脂肪脂解酶。此外，用白细胞介素-6预处理3T3-L1细胞，然后用重组人FGF21（rhFGF21）处理；评估脂解情况。
结果
DSS显著降低了eWAT/体重比，增加了血清游离脂肪酸（FFA）和甘油浓度，表明脂肪组织脂解增加。eWAT细胞内脂解酶的表达/激活显著增加。在FGF21基因敲除小鼠中以及通过循环FGF21中和，这些改变显著减弱。此外，DSS处理显著增加了血清白细胞介素-6和FGF21水平。白细胞介素-6预处理是FGF21对3T3-L1细胞脂肪脂解刺激作用所必需的。
结论
我们的结果表明，实验性结肠炎通过白细胞介素-6/FGF21介导的信号通路诱导eWAT脂解。
Zotero 插件