The role of nicotinamide nucleotide transhydrogenase mitochondrial (NNT) on the glycemic homeostasis and lipidic: study in C57BL6 mice

Author(s)

Juliana Cristine Rovani

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2014-02-14

Examining board members

Helena Coutinho Franco de Oliveira; Everardo Magalhães Carneiro; Tiago Rezende Figueira

• Advisor: Helena Coutinho Franco de Oliveira

Abstract

The nicotinamide nucleotide transhydrogenase (NNT) catalyses the production of NADPH, that is consumed by the mitochondrial antioxidant enzymatic system. Previous studies have shown that NNT mutation causes redox abnormalities in mitochondria and alterations in glucose and lipid metabolism in C57BL6/J mice from The Jackson Laboratory. Metabolic syndrome is characterized by an association of cardio-metabolic disturbances such as visceral obesity, dyslipidemias, glucose intolerance and/or insulin resistance and hypertension. Caloric restriction has been recommended to prevent or treat such metabolic disturbances. Synthetic compounds have been tested as putative mimetic for caloric restriction. The 2,4 dinitrophenol (DNP) is one of this drugs that increase the metabolic rates due to a reduction in the oxidative phosphorylation efficiency and elevation of oxidative metabolism. In this study we demonstrated that mice that carry a NNT gene mutation (B6-J) exhibit increased visceral adiposity, increased liver triglyceride content, glucose intolerance, insulin resistance, and insulin hypersecretion, when compared to control mice with functional NNT. In face of these disturbances, mutant B6-J mice were submitted to a food restriction (FR) or treatment with DNP during 3 months. We observed that B6-J mutant mice under FR present a reduction in adiposity and liver steatosis, improvement of glucose tolerance and insulin resistance and normalization of insulin secretion. After DNP treatment, B6-J mice showed no alterations in lipid disturbances but improved insulin resistance and insulin secretion. These findings suggest that 1- the mouse substrain that carries NNT mutation is predisposed to develop metabolic syndrome, 2- both treatments, FR and DNP, correct, at least partially, the metabolic disturbances of B6-J mutant mice, and 3- FR treatment was more effective than DNP (AU)

• FAPESP's process: 11/14521-7 - Role of mitochondrial transhydrogenase in the metabolic response to caloric restriction and mitochondrial uncoupling in mice
• Grantee: Juliana Cristine Rovani Rodrigues
• Support Opportunities: Scholarships in Brazil - Master