Investigation of glucose and lipid metabolism alterations in a model of nicotinamide nucleotide transhydrogenase mitochondrial (NNT)deficiency

• Grant number: 14/02819-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): April 01, 2014
• Effective date (End): February 28, 2018
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Helena Coutinho Franco de Oliveira
• Grantee: Juliana Cristine Rovani Rodrigues
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Our recent studies comparing two C57BL6 mice strains with or without deficiency of mitochondrial nicotinamide nucleotide transhydrogenase (NNT) revealed that the absence of NNT is associated with increased adiposity, hepatic steatosis, glucose intolerance and hyperinsulinemia (insulin resistance) and insulin hypersecretion. Furthermore, an increase of total insulin content in pancreatic islets of NNT deficient mice was observed. The phenotype characterization obtained, known as metabolic syndrome, is positively associated with high risk of vascular diseases. In a metabolic syndrome, a chronic state of subclinical inflammation and oxidative stress is also observed. NNT is a mitochondrial enzyme that produces NADPH from NADP+ and NADH, and play a significant role in the maintenance of mitochondrial bioenergetic and redox functions. Reduction of NADPH (in NNT deficiency) causes decreased GSH/GSSG ratio, reducing the antioxidant capacity and increasing the generation of reactive oxygen species in mitochondria. Our hypothesis is that NNT deficiency causes oxidative stress, which contributes to the genesis of glucose and lipid metabolism disorders. Therefore, the objective of this project is to study the cellular and molecular mechanisms involved in the effect NNT deficiency on the glucose homeostasis and adiposity in C57BL6/J (Jackson Lab, NNT deficient) and C57BL6/JUnib, (CEMIB-Unicamp, NNT intact).

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NAVARRO, CLAUDIA D. C.; FIGUEIRA, TIAGO R.; FRANCISCO, ANNELISE; DAL'BO, GENOEFA A.; RONCHI, JULIANA A.; ROVANI, JULIANA C.; ESCANHOELA, CECILIA A. F.; OLIVEIRA, HELENA C. F.; CASTILHO, ROGER F.; VERCESI, ANIBAL E. Redox imbalance due to the loss of mitochondrial NAD(P)-transhydrogenase markedly aggravates high fat diet-induced fatty liver disease in mice. Free Radical Biology and Medicine, v. 113, p. 190-202, DEC 2017. Web of Science Citations: 9.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RODRIGUES, Juliana Cristine Rovani. Role of mitochondrial nicotinamide nucleotide transhydrogenase in glucose and lipids metabolism. 2018. Doctoral Thesis - Universidade Estadual de Campinas, Instituto de Biologia.