Effects of treatment with Liraglutide in signaling pathways of insulin and leptin in the hypothalamus of DIO mice

Author(s)

Giovanna Tase Ricardo

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2015-10-30

Examining board members

Patrícia de Oliveira Prada; Any Elisa de Souza Schmidt Gonçalves; Michella Soares Coelho

• Advisor: Patrícia de Oliveira Prada

Abstract

Glucagon-like peptide 1 (GLP-1), one of the major hormones synthesized by the intestine, is released in response to the presence of nutrients in the gastrointestinal tract. Its receptors are expressed in neurons of the central nervous system (CNS) in regions such as the hypothalamus and the central nucleus of the amygdala (CeA), involved in the modulation of feeding behavior and body weight maintenance. Liraglutide is a drug which mimetizes GLP-1 hormone leading to loss of weight and therefore has been used in the treatment of type 2 diabetes mellitus (T2DM). Mechanisms of action in the CNS of anorexia induction have not been completely understood. The present study aimed to investigate whether treatment with liraglutide influence body weight modulating and insulin and leptin sensitivity in the hypothalamus and CeA of mice with obesity induced by high fat diet (DIO). Swiss mice received high fat diet for 8 weeks and had a cannula implanted in one of the lateral ventricles. Then animals were treated with liraglutide or vehicle intraperitoneally for 8 days (200 µg/kg/day). Body weight was monitored daily and food intake was measured after intracerebroventricular injections (ICV) of insulin or leptin. On the last day of treatment, after overnight fasting, were evaluated body weight, fasting blood glucose and body fat mass. After 15 minutes of ICV injection of insulin or leptin were extracted: hypothalamus, CeA, white and brown adipose tissue. These tissues were processed for investigation of the expression/phosphorylation of proteins participants on insulin and leptin signaling pathway by immunoblotting. The animals subjected to the treatment showed a significant decrease in adiposity, fasting glucose, increased O2 consumption and reduced food intake. Furthermore, animals treated with liraglutide showed higher phosphorylation of different proteins in the intracellular signaling pathway of insulin and leptin in the hypothalamus and CeA. Our results suggest that liraglutide improves the action and signaling of insulin and leptin in the hypothalamus and amygdala of DIO mice. This improvement contributed to the reduction of food intake and adiposity associated with increased energy expenditure (AU)

• FAPESP's process: 13/10493-4 - Study of molecular mechanisms involved in the reduction of obese rodents treated with liraglutide
• Grantee: Giovanna Tase Ricardo
• Support Opportunities: Scholarships in Brazil - Master