Acute Effects of Glucagon-Like Peptide-1 on Hypothalamic Neuropeptide and AMP Activated Kinase Expression in Fasted Rats

Endocrine Journal

Sunghee JU¹  Hyunju CHUNG¹  Sanghee SEO¹  Dahm LEE¹  Seungjoon PARK¹ 

[1] Department of Pharmacology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, Kyunghee University School of Medicine

关键词: GLP-1;    Food deprivation;    Hypothalamus;    Neuropeptide;    AMPK;   

DOI  :  10.1507/endocrj.K08E-091

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(35)Cited-By(36)Intracerebroventricular (icv) administration of glucagon-like peptide-1 (GLP-1) inhibits food intake and induces c-fos expression in the hypothalamus. However, the effects of GLP-1 on hypothalamic neuronal activity or neuropeptide mRNA expression are unknown. In this study, we examined the effects of GLP-1 on fasting-induced changes in the expression of hypothalamic orexigenic and anorexigenic neuropeptide. Food intake was significantly inhibited after icv injection of GLP-1 in 48 h fasted rats. Hypothalamic neuropeptide Y (NPY) and agouti-related peptide (AgRP) mRNAs were significantly increased by fasting, whereas icv GLP-1 treatment significantly attenuated these fasting-induced increases. Both proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA levels were decreased by fasting, while GLP-1 treatment attenuated fasting-induced decreases in POMC and CART expression. We also determined the mRNA levels of AMP-activated kinase (AMPK) and found that fasting resulted in a significant stimulation of hypothalamic AMPKα2 mRNA. Fasting-induced increase in AMPKα2 mRNA was almost completely prevented by GLP-1 treatment. Analysis of phosphorylated AMPKα and acetyl CoA carboxylase showed similar results. Taken together, our observation suggests that the decreased food intake by GLP-1 is caused by preventing the fasting-induced increase in hypothalamic NPY and AgRP and the fasting-induced decrease in hypothalamic POMC and CART. Our results also suggest that the food intake lowering effect of GLP-1 is caused by reversing the fasting-induced increase in hypothalamic AMPK activity. Therefore we conclude that the anorectic effect of GLP-1 seems to be mediated by, at least in part, by the hypothalamus.

【 授权许可】

Unknown