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Evaluation of the relationship between weight gain, ectopic fat accumulation in the liver and hepatic expression of miR-122, miR-370 and Let-7 in mice fed with HFD for different periods

Grant number: 17/09277-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2017
Effective date (End): November 14, 2018
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal Investigator:Adriana Souza Torsoni
Grantee:Carolina Panzarin
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

The number of obese in the world population is directly associated with the increase in the prevalence of Non Alcoholic Fatty Liver Disease (NAFLD), condition in which there is accumulation of triglycerides (TAG) in the liver, which can lead to non-alcoholic steatohepatitis (NASH), with progression to fibrosis, cirrhosis and hepatocarcinoma. It is known that hepatic lipid metabolism can be regulated through expression of microRNAs (miRs). MiR-122, the most expressed in the liver, has several functions, among them its performance in the lipidic and glucose metabolism. In miR-122 knockout mice, an increase of hepatic TAG was observed through the positive regulation of genes involved in the biosynthesis and storage of them. MiR-122 expression is controlled by another miR, miR-370, which affects lipid metabolism also by decreasing CPT1 expression. Let-7, a well known miR, and Lin28, protein responsible for its modulating function in processing, are involved with glucose metabolism. Lin28 is related to increased production of mitochondrial enzymes as well as peripheral insulin sensitivity. Considering the impact of these microRNAs on the development of obesity and its comorbidities, the aim of the present study was to investigate, in mice submitted to HFD for different periods, the possible cause and effect relationship between the development of NAFLD and the alteration in miR-122, miR-370 and Let-7 expression in the liver. (AU)