Impact of microRNA-22 and cellular senescence in obesity-induced metabolic dysfunctions

• Grant number: 20/13211-3
• Support type: Regular Research Grants
• Duration: August 01, 2021 - July 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal researcher: Gabriela Placoná Diniz
• Grantee: Gabriela Placoná Diniz
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Obesity is a risk factor for development of several diseases. Recent studies indicate that high-fat diet-induced obesity increases cellular senescence in white adipose tissue, and that depletion of senescent cells reduces some cardiovascular and metabolic alterations caused by obesity. Although obesity stimulates cellular senescence, little is known about the mechanisms involved in high-fat diet-induced cellular senescence in white adipose tissue. MiRNA-22 is one of the mechanisms related to control of cellular senescence. Previous studies of our group identified that miRNA-22 deletion attenuates obesity-induced white adipose tissue gain and prevents dyslipidemia. Given that miRNA-22 and high-fat diet stimulate cellular senescence, this study aims to characterize the impact of miRNA-22 in obesity-induced white adipose tissue cellular senescence and metabolic dysfunctions. To address this question, wild type and miRNA-22 knockout mice will be induced to obesity and white adipose tissue cellular senescence profile will be characterized by molecular analyses. To evaluate whether the depletion of senescent cells is able to potentialize the effects promoted by miRNA-22 deletion in obesity, wild type and miRNA-22 knockout mice will be induced to obesity and treated with senolytics. To investigate whether white adipose tissue of obese mice secrets molecules able to influence metabolic dysfunctions, and whether miRNA-22 is able to modulate this effect, we will perform experiments of white adipose tissue transplant from obese mice, with or without miRNA-22, into receptor mice that will be induced to obesity. Moreover, to characterize directly the impact of miRNA-22 in cellular senescence, we will use 3T3-L1 cells with miRNA-22 deletion by CRISPR/Cas9. (AU)