Control of Rev-erb-alpha expression after disruption of circadian rhythm

• Grant number: 16/04314-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 01, 2016
• End date: May 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Everardo Magalhães Carneiro
• Grantee: Patricia Cristine Borck
• Supervisor: Mitchell A. Lazar
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Pennsylvania, United States
• Associated to the scholarship: 13/26740-0 - Molecular and functional analysis of the mechanism of secretion and insulin action in malnourished mice subjected to continuous exposure to light, BP.DR

Abstract

Circadian rhythm is an adaptative mechanism that prepares the organism to respond to chances in environmental conditions. In mammals, the biological clock is generated endogenously in the suprachiasmatic nucleus of the hypothalamus, and the light is one of the most important synchronizer of this circadian system. Disruption of the circadian rhythm, by exposure to light at night, due shift work, and jet lag is related with increased prevalence of obesity and type 2 diabetes (T2D). In both pathologies, the expression of clock genes are altered, specially, Rev-erb± which controls the lipid metabolism in liver. We found that mice, submitted to constant light, showed increased in body and fat pad weights, impairment of the expression of Rev-erb±, and higher levels of triglycerides in the liver. In addition, the expression of proteins, involved with de novo lipogenic pathway, was increased. Taking into account the association between the expression of Rev-erb± and the development of metabolic disease, more studies are necessary in order to understand the mechanisms that regulate the expression of this clock gene. Recently, it was demonstrated that the expression of clock genes can be modulated by post-transcriptional mechanism, additionally to the transcriptional process. In this context, and as already observed for other clock genes, a new class of post-transcriptional regulators, the microRNAs, could be associated with the reduced of Rev-erb± expression. Thus, the aim of this project is to study the control of the Rev-erb± expression by microRNAs, in mice with disruption of the circadian rhythm by continuous exposure to light. (AU)