Contribution of adipose tissue miRNAs in cardiac function, metabolism and remodeling

• Grant number: 19/21852-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2020
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Henver Simionato Brunetta
• Host 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
• Associated scholarship(s): 22/00358-1 - Crosstalk between adipocyte-derived miRNA-802 and heart GATA4: a potential novel endocrine mechanism controlling heart remodeling and function, BE.EP.PD

Abstract

Obesity and overweight are risk factors for the development of cardiovascular diseases. Importantly, cardiovascular diseases are the main cause of death worldwide, being responsible for around 31% of all deaths. Although initially thought as an energy storage tissue, adipose tissue is now recognized as an important endocrine organ. Adipose tissue communicates with other organs via hormones called adipokines, and as more recently demonstrated, via microRNAs (miRNAs). Our group has shown that the expression of DICER, an important protein involved in miRNAs processing, in adipose tissue, is altered in Obesity and aging. Indeed, adipose tissue-specific Dicer deletion in mice leads to insulin resistance, metabolic alterations in non-adipose tissues and premature aging. These data strongly evidence the crosstalk between adipose tissue and other organs via miRNAs. Cardiac tissue is able to use several different substrates; indeed, metabolic flexibility is closely associated with heart function. In addition, cardiac remodeling, as observed in hypertension, leads to alteration in cardiomyocyte metabolism. However, even with the well-established relationship between adipose tissue function and cardiovascular diseases, it is still not clear if miRNAs from adipose tissue play a role in cardiac function, whether in physiologic or pathologic scenarios. The aim of the present study is to investigate the crosstalk between adipose tissue and heart via miRNAs using an adipocyte-specific Dicer knockout mouse. Our hypothesis is that miRNAs from adipose tissue play a role in cardiac metabolism and function. Moreover, adipose tissue miRNAs could participate in cardiac remodeling during hypertension. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TOWNSEND, LOGAN K.; BRUNETTA, HENVER S.; MORI, MARCELO A. S.. Mitochondria-associated ER membranes in glucose homeostasis and insulin resistance. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 319, n. 6, p. E1053-E1060, DEC 2020. (17/01184-9, 19/21852-1)

MIOTTO, PAULA M.; DAO, GIANG M.; BRUNETTA, HENVER S.. Fission accomplished: Uncovering the role of Drp1 in regulating mitochondrial dysfunction and age-related muscle atrophy. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 21, p. 3-pg., 2021-10-10. (19/21852-1)

BRUNETTA, HENVER S.; HOLLOWAY, GRAHAM P.. A theoretical argument to support the biological benefits for insulin stimulating mitochondrial oxidative phosphorylation. CURRENT OPINION IN PHYSIOLOGY, v. 25, p. 6-pg., 2022-02-01. (19/21852-1)