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Role of mitochondrial transhydrogenase in the metabolic response to caloric restriction and mitochondrial uncoupling in mice

Grant number: 11/14521-7
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2014
Field of knowledge:Biological Sciences - Physiology - General 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


The metabolic syndrome incidence has risen rapidly worldwide and is characterized by the presence of at least three metabolic disturbances simultaneously among obesity, dyslipidemia, hypertension, glucose intolerance and / or insulin resistance. Scientific evidences have shown that caloric restriction increases longevity and reduces the risk of chronic diseases, and thus, may be used for preventing or treating these metabolic disorders. Our recent results demonstrated that hypercholesterolemic LDL receptor deficient mice (LDLR0) submitted to caloric restriction (CR) presented improved glucose tolerance but worsened plasma lipid profile and body fat content. However, in addition to the LDL receptor defect, these mice present another genetic mutation in the nicotinamide nucleotide transidrogenase (NNT) gene. This mutation has been pointed as responsible for variations in metabolic responses in genetically modified mice with different genetic backgrounds. Thus, the objective of this study is to evaluate whether the prejudicial effects of CR observed in LDLR0 were responses linked to the specific LDL receptor defect that causes hypercholesterolemia or are also present in the normolipidemic mice with NNT deficiency only. In addition, we will use a treatment with dinitrophenol (DNP) considered a CR mimetic, which targets mitochondria. Therefore, we will use C57BL6/uni isogenic mice (intact NNT) from CEMIB-Unicamp and mice C57BL6 /J (mutant NNT) from Jackson Laboratory, where we observe macroscopic differences in adiposity. Besides these groups, we will also work with a Swiss heterogenetic mice line from CEMIB, which is considered, as the previous ones, susceptible to obesity, diabetes and atherosclerosis induced by diet.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RODRIGUES, Juliana Cristine Rovani. The role of nicotinamide nucleotide transhydrogenase mitochondrial (NNT) on the glycemic homeostasis and lipidic : study in C57BL6 mice. 2014. Master's Dissertation - Universidade Estadual de Campinas. Instituto de Biologia.

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