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Comparative study on anorexigenic effect of glucagon-like peptide-1 receptor agonists in rats

WEN Song, Thiquynhnga NGUYEN, XIAO Wen-Ze, WANG Chao-Xun, GONG Min, JIN Jian-Lan, ZHOU Li-Gang^*

Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, China

Abstract

Glucagon-like peptide-1 (GLP-1) expression is shared by both intestinal cells and neurons of brainstem, which plays anorexigenic role on food intake. However, the exact source of physiological GLP-1 influencing food intake and pertinent mechanism of GLP-1 receptor agonists (GLP-1RA) remain unelucidated.  In this study, the immediate early gene product c-Fos was chosen as the specific antigen for immunohistochemistry to show the certain areas of central nervous system (CNS) activation by the GLP-1RA. Thirty normal SD rats were randomly assigned to 3 groups, which were single intraperitoneally injected with Liraglutide (200 μg/kg), Exenatide (10 μg/kg) and saline, respectively. After injection, the amount of food intake and acute glycemic variation were assessed for comparison. The results showed that acute pharmacological dosage of GLP-1RA (Liraglutide or Exenatide) could significantly influence food intake. However, glycemic change indicated that the anorexic effect was dissociated with change in blood glucose in normal rats. Moreover, c-Fos was expressed significantly higher in major critical nuclei related to food intake in GLP-1RA groups when compared with the control group, and its expression was also found in spinal cord. The results suggested that acute administration of pharmacological doses of GLP-1 influences CNS via circulation and vagal pathways, especially on the arcuate nucleus (ARC) and the nucleus of solitary tract (NTS), and GLP-1 modulates autonomic nervous activities. 

Key words: glucagon-like peptide-1; c-Fos; food intake; brain nuclei; spinal cord

Received: 2019-01-14　　Accepted: 2019-03-12

Corresponding author: 周里钢　　E-mail: zhouligang@yahoo.com

DOI: 10.13294/j.aps.2019.0043

Citing This Article：

WEN Song, Thiquynhnga NGUYEN, XIAO Wen-Ze, WANG Chao-Xun, GONG Min, JIN Jian-Lan, ZHOU Li-Gang. Comparative study on anorexigenic effect of glucagon-like peptide-1 receptor agonists in rats. Acta Physiol Sin 2019; 71 (4): 514-526