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Abstract |
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| Vol 46 No. 8: 675-681 |
[PDF] [Full Text] |
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| The anorexic effect of Ex4/Fc through GLP-1 receptor activation in high-fat diet fed mice |
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| Rui Liu1,2,
Duan Ma3,
Yiming Li2,
Renming Hu2,
Yongde Peng1 and
Qinghua Wang2,4,*
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1Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China
2Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai 200040, China
3Key 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
4Division 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 1W8, Canada
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Abstract Exendin-4 (Ex4), a peptide initially found in the saliva of the Gila monster, can activate the signaling pathway of the incretin 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 expression of Ex4/Fc by intramuscular injection of the plasmid encoding 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. Interestingly, 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. |
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Keywords exendin-4 (Ex4); glucagon-like peptide-1 (GLP-1); high-fat diet (HFD); obesity; diabetes |
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Received 2013-12-1
Accepted 2014-4-18 |
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Funding 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). |
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* Correspondence address Tel: +1-416-864-6060 (Ext. 77610); Fax: +1-416-864-5140; E-mail: [email protected] |
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