中链脂肪酸受体GPR84对小鼠糖脂代谢的影响  

Effect of Medium-chain Fatty Acid-sensing Receptor GPR84 on Glucose and Lipid Metabolism in Mice

作　　者：方友臣 郑洋 张庆 李静 谢欣[2] FANG You-Chen;ZHENG Yang;ZHANG Qing;LI Jing;XIE Xin(School of Life Sciences Shanghai University,Shanghai 200444,China;The National Center for Drug Screening,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;ShanghaiTceh University,Shanghai 201210,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]上海大学生命科学学院,上海200444 [2]中国科学院上海药物研究所国家新药筛选中心,上海201203 [3]上海科技大学,上海201210 [4]中国科学院大学,北京100049

出　　处：《生物化学与生物物理进展》2018年第8期853-864,共12页Progress In Biochemistry and Biophysics

基　　金：国家重点基础研究计划(973计划)(2014CB541900);国家杰出青年科学基金项目(81425024);国家自然科学基金面上项目(81573442)资助~~

摘　　要：目前,全球肥胖及肥胖引发的并发症如2型糖尿病、心血管疾病等患病率呈上升趋势,并逐渐成为一个重大的公共卫生问题.与肥胖相关疾病的发病机制是由多种因素共同作用的结果,游离脂肪酸受体在其中就扮演着重要角色.G蛋白偶联受体84(GPR84)是中链脂肪酸(C9-C14)受体,其在糖脂代谢方面的功能尚不清楚.因此,探究中链脂肪酸受体GPR84在小鼠糖脂代谢方面的作用,具有重要意义.本文利用高脂饲料在GPR84野生型(WT)和基因敲除型(GPR84^(-/-))小鼠中诱导肥胖模型.研究发现,在常规饲料(normal chow,NC)喂养组和高脂饲料(high-fat diet,HFD)喂养组,与WT小鼠相比,GPR84^(-/-)小鼠在体重、摄食量、葡萄糖耐量、胰岛素敏感性、空腹血糖值、血清中胰岛素含量、组织器官重量、脂质合成与脂肪酸氧化、白色脂肪形成方面无显著性差异;在血脂水平,GPR84^(-/-)小鼠与WT小鼠相比,甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇无显著性差异;但是在高脂饲料喂养组,GPR84^(-/-)小鼠总胆固醇浓度显著性降低.同时,我们发现,在HFD组,与WT小鼠相比,GPR84^(-/-)小鼠肝脏中B类Ⅰ型清道夫受体表达显著上调.综上所述,中链脂肪酸受体GPR84在高脂诱导的肥胖模型中不影响小鼠糖脂代谢,但可能在由高胆固醇引起的高胆固醇血症发挥一定的功能.The global rise of obesity and obesity-associated complications such as type 2 diabetes and cardiovascular disease has become a major public health concern. The etiology and pathogenesis of these obesityrelated diseases are caused by multiple factors, and the free fatty acid receptors may play important roles. G protein coupled receptor 84（GPR84） is a medium-chain（C9-C14） fatty acid-sensing receptor. However, its functions in obesity and metabolic diseases remain unclear. In this research, we established a high-fat diet induced obesity model in wild type and GPR84 knockout mice. Compared with WT mice, GPR84 knockout mice have similar levels of food intake, body weight, oral glucose tolerance test and insulin tolerance test both on normal chow diet and high-fat diet. GPR84 deficiency in mice did not affect fasting blood glucose level, insulin, triglyceride, low density lipoprotein cholesterol（LDL-c） and high density lipoprotein cholesterol（HDL-c）. There were no genotypic differences in tissue mass, lipid synthesis, fatty acid oxidation and lipogenesis in mice on normal chow diet or high-fat diet. However, the concentration of total cholesterols（TC） was significantly reduced and scavenger receptor class B typeⅠ（SR-BⅠ） was significantly increased in GPR84 knockout mice compared with WT mice on high-fat diet. These results indicate that GPR84 may not be involved in glucose and lipid metabolism in mice;instead, it may play a role in hypercholesterolemia caused by high cholesterol.

关 键 词：GPR84 中链脂肪酸受体 肥胖 脂类代谢 高胆固醇血症 

分 类 号：R589.2[医药卫生—内分泌] Q493.9[医药卫生—内科学]