Potential role of hypothalamic AMPK for fructose-induced modulation of gluconeogenesis

• Grant number: 11/10547-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2011
• End date: September 30, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Silvana Auxiliadora Bordin da Silva
• Grantee: Silvana Auxiliadora Bordin da Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Gabriel Forato Anhê

Abstract

Fructose-enriched diets are known to cause several metabolic adaptations associated with metabolic syndrome such as increased fasting glycemia, insulin resistance and increased circulating triglycerides with hepatic steatosis. Many studies describe that fructose causes hepatic insulin resistance and increase of gluconeogenesis through mechanisms yet unknown. The importance of extra-hepatic regulation of gluconeogenesis mainly that generated from the hypothalamus was recently demonstrated to be an important event in the pathophysiology of Type 2 Diabetes. In parallel, other studies demonstrate that fructose induces food intake due to activation of AMPK in the central nervous system. Still in this topic, it was recently demonstrated that AMPK induced neuronal depolarization via activation of nNOS. Nitric oxide, in turns, activates guanylyl cyclase that reduces cellular permeability to Cl-. The aim of the present study is to investigate whether the activation of the hypothalamic AMPK/nNOS/GCs pathway induced by fructose may control food intake and gluconeogenesis. Wistar rats will be submitted to canulla implantation in the lateral ventricle. Through this canulla, Fructose, L-NAME, Compound C, AICAR and ODQ will be injected. After treatments, liver and hypothalamus will be used for western blot detection of pAMPK, pACC, pnNOS, pCFTR, PEPCK and G6PASE. Intraperitoneal pyruvate tolerance test will be performed in order to determine gluconeogenesis rate. Hypothalamus will be used to assess cGMP levels. (AU)