The anorexic effect of Ex4/Fc through GLP-1 receptor activation in high-fat diet fed mice  

作　　者：Rui Liu Duan Ma Yiming Li Renming Hu Yongde Peng Qinghua Wang 

机构地区：[1]Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China [2]Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai 200040, China [3]Key Laboratory of Metabolic Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology,Institute of Medical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai 200030, China [4]Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science of St. Michael's Hospital,Departments of Physiology and Medicine, University of Toronto, Toronto M5B lW8, Canada

出　　处：《Acta Biochimica et Biophysica Sinica》2014年第8期675-681,共7页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Basic Research Program of China （No. 2006CB503908） and National Natural Science Foundation of China （No. 81200622 and No. 81100616）, and the Juvenile Diabetes Research Foundation （1-2006-275）.

摘　　要：Exendin-4 （Ex4）, a peptide initially found in the saliva of the Gila monster, can activate the signaling pathway of the incre- tin hormone glucagon-like peptide-1 （GLP-1） through the GLP-1 receptor （GLP-1R）. We previously reported that a chimera protein consisting of Ex4 and mouse IgG heavy chain constant regions （Ex4/Fc） can exert biological effects of GLP-1, such as improving glycemic control and ameliorating manifestations in diabetic mice. The aim of this study was to determine whether Ex4/Fc is effective in modulating energy homeostasis in mice. Our results showed that in vivo expres- sion of Ex4/Fc by intramuscular injection of the plasmid en- coding Ex4/Fc followed by local electroporation effectively decreased food intake in the mice on high-fat diet （HFD） feeding. In addition, the reduced energy intake was associated with the decreased excrements from the Ex4/Fc-treated HFD mice but not the Fc control mice. Remarkably, the Ex4/Fc- treated HFD mice displayed significantly lower triglyceride （TG） levels when compared with the control mice. Interest- ingly, while the leptin levels were not changed, the circulating ghrelin levels were higher in Ex4/Fc mice than those in the Fc control mice. These results suggested that Ex4/Fc can improve energy metabolism and lipid metabolism through GLP-1R in mice under excessive nutrition conditions.Exendin-4 （Ex4）, a peptide initially found in the saliva of the Gila monster, can activate the signaling pathway of the incre- tin hormone glucagon-like peptide-1 （GLP-1） through the GLP-1 receptor （GLP-1R）. We previously reported that a chimera protein consisting of Ex4 and mouse IgG heavy chain constant regions （Ex4/Fc） can exert biological effects of GLP-1, such as improving glycemic control and ameliorating manifestations in diabetic mice. The aim of this study was to determine whether Ex4/Fc is effective in modulating energy homeostasis in mice. Our results showed that in vivo expres- sion of Ex4/Fc by intramuscular injection of the plasmid en- coding Ex4/Fc followed by local electroporation effectively decreased food intake in the mice on high-fat diet （HFD） feeding. In addition, the reduced energy intake was associated with the decreased excrements from the Ex4/Fc-treated HFD mice but not the Fc control mice. Remarkably, the Ex4/Fc- treated HFD mice displayed significantly lower triglyceride （TG） levels when compared with the control mice. Interest- ingly, while the leptin levels were not changed, the circulating ghrelin levels were higher in Ex4/Fc mice than those in the Fc control mice. These results suggested that Ex4/Fc can improve energy metabolism and lipid metabolism through GLP-1R in mice under excessive nutrition conditions.

关 键 词：exendin-4 （Ex4） glucagon-like peptide-1（GLP-1） high-fat diet （HFD） OBESITY DIABETES 

分 类 号：Q959.837[生物学—动物学] S511[农业科学—作物学]