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The role of mitonuclear imbalance and hypothalamic UPRmt on the control of food intake of obese mice

Grant number: 19/21171-4
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): August 01, 2020
Effective date (End): May 31, 2024
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Eduardo Rochete Ropelle
Grantee:Renata Rosseto Braga
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

The prevalence of overweight and Obesity is increasing over the years and one of the main causes is the lifestyle that is currently being adopted by the population. Excessive consumption of saturated fat alters the functionality of hypothalamic neurons that control energy homeostasis. Mitochondrial activity in neurons of the arcuate nucleus of the hypothalamus is closely related to the control of food intake and energy homeostasis. Studies have shown that Obesity culminates in damage to the functioning of this organelle, presenting a reduction in the expression of genes from mitochondrial DNA and consequently affects its function. In stressful situations the cellular environment can acquire a proteotoxic characteristic through the accumulation of malformed proteins. Given this, there is the development of a highly conserved mechanism between species to reestablish cellular proteostasis, called mitochondrial Unfolded Protein Response (UPRmt). In this scenario, we hypothesized that treatment with a high-fat diet may induce a stoichiometric difference in the ratio of protein expression from nuclear DNA to protein derived from mitochondrial DNA, called mitonuclear imbalance, and thus trigger UPRmt in mouse hypothalamus, culminating in alterations in hypothalamic control of food intake and energy metabolism. The development of the current project may provide new insights into the effects of high-fat diet on the functioning of mitochondria in hypothalamic neurons. (AU)