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Daily rhythm changes in Dicer expression in adipose tissue and the impact over metabolism

Grant number: 16/17075-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2018
Effective date (End): December 31, 2020
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Marcelo Alves da Silva Mori
Grantee:Juliano Quintella Dantas Rodrigues
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics, AP.TEM

Abstract

Nowadays, the increasing prevalence of obesity among adults and children are major problems of global health. Obesity increases the risk of metabolic and cardiovascular diseases such as diabetes, heart failure and hypertension. On the other hand, caloric restriction reduces these risks and extends health span. Studies from our group and other groups have shown that with obesity in mice there is a decrease in the expression of Dicer and miRNAs in adipose tissue. The opposite occurs with caloric restriction, where Dicer and miRNAs are up regulated in adipose tissue. Dicer is a type III endoribonuclease that plays a key role in the processing of double-stranded RNA (dsRNA), cleaving these molecules into small fragments of about 20 nucleotides, including miRNAs. Some studies have shown that Dicer has a tissue specific daily rhythms regulation (liver and suprachiasmatic nucleolus) and changes in this pattern lead to the emergence of metabolic diseases such as type 2 diabetes. So far we do not know if the expression of Dicer is regulated by daily variation in adipose tissue of mice. This tissue exerts an important role in organismal metabolism and Dicer participates in this process. In fact, fat-specific Dicer knockout mice, using the Cre/LoxP strategy, (AdicerKO) exhibit lipodystrophy, insulin resistance, hypersensitivity to oxidative stress among others pathophysiological complications. Thus, it is interest to verify whether the Dicer enzyme is expressed rhythmically in adipose tissue, and whether that profile is regulated by the diet or by the endogenous timer system mediated by BMAL1. In addition, we will study if the loss of Dicer or BMAL1 function in adipocytes affects the endocrine rhythm of the animal, which would suggest a role of the adipocyte, and in particular of Dicer, in the control of metabolic rhythm.