Role of microRNA-22 in the development of cardiac and metabolic alterations induced by high fat diet

• Grant number: 15/21859-5
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2016
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Gabriela Placoná Diniz
• Grantee: Gabriela Placoná Diniz
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Obesity is considered a major risk factor for developing cardiovascular diseases and diabetes. In this sense, it is essential not only to increase the understanding of the biological mechanisms involved in cardiac alterations evidenced in obesity, but also to identify potential treatments able to atenuate the cardiac structural and functional alterations, as well as metabolic alterations that these individuals present.Several recent studies revealed the important role of microRNAs (miRNAs) in the control of cardiac structrure and function, as well as in the development of diverse cardiovascular and metabolic diseases. In this sense, our laboratory recently demonstrated that cardiac hypertrophy induced by high fat diet is accompanied by alteration on miRNAs expression pattern in the heart (Guedes et al., submitted). However, the potential functional role of these miRNAs for the development of hypertrophy and compromised cardiac function elicited by high fat diet remains unknown. Recently, we identified the miRNA-22 among the most upregulated miRNAs in cardiac remodeling induced by high fat diet. Recent studies demonstrated that miRNA-22 plays a key role in hypertrophy and cardiac dysfunction induced by several stimuli, including pressure overload, angiotensin II and phenilephrine. Considering that miRNA-22 is involved in the development of cardiac remodeling evidenced in some models, and that its expression is increased in cardiac hypertrophy mediated by high fat diet, it is essential to carachterize the functional role of miRNA-22 in the cardiac morphological and functional alterations induced by high fat diet. Aditionally, considering that some miRNAs play an important role in body weigh gain and in the insulin resistance induced by high fat diet, and that miRNA-22 targets PGC1± e PPAR±, which are genes involved in metabolic processes and mitochondrial function, it is essential to determine the functional role of miRNA-22 in the metabolic alterations elicited by high fat diet. In this sense, the present study aims to caractherize the contribution of miRNA-22 in cardiac structural and functional alterations induced by high fat diet, by using knockout mice for miRNA-22. Moreover, this study will caractherize the functional role of miRNA-22 in metabolic alterations elicited by high fat diet. (AU)

Scientific publications

(5)

(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)

GUEDES, ELAINE CASTILHO; DA SILVA, IVSON BEZERRA; LIMA, VANESSA MORAIS; MIRANDA, JULIANE B.; ALBUQUERQUE, RUDA P.; FERREIRA, JULIO C. B.; BARRETO-CHAVES, MARIA LUIZA M.; DINIZ, GABRIELA PLACONA. High fat diet reduces the expression of miRNA-29b in heart and increases susceptibility of myocardium to ischemia/reperfusion injury. Journal of Cellular Physiology, v. 234, n. 6, p. 9399-9407, JUN 2019. (15/21859-5, 17/16694-2, 13/05742-5)

DINIZ, GABRIELA PLACONA; HUANG, ZHAN-PENG; LIU, JIANMING; CHEN, JINGHAI; DING, JIAN; FONSECA, RENATA INZINNA; BARRETO-CHAVES, MARIA LUIZA; DONATO, JR., JOSE; HUI, XIAOYUN; WANG, DA-ZHI. Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy. Clinical Science, v. 131, n. 24, p. 2885-2900, DEC 15 2017. (15/21859-5, 14/50140-6)

LIMA, VANESSA M.; LIU, JIANMING; BRANDAO, BRUNA B.; LINO, CAROLINE A.; SILVA, CAMILA S. BALBINO; RIBEIRO, MARCIO A. C.; OLIVEIRA, TIAGO E.; REAL, CAROLINE C.; FARIA, DANIELE DE PAULA; CEDERQUIST, CARLY; et al. miRNA-22 deletion limits white adipose expansion and activates brown fat to attenuate high-fat diet-induced fat mass accumulation. METABOLISM-CLINICAL AND EXPERIMENTAL, v. 117, APR 2021. (17/01558-6, 15/21859-5, 18/10338-2, 17/26528-2)

LIMA, VANESSA MORAIS; FONSECA, RENATA INZINNA; WANG, DA-ZHI; DINIZ, GABRIELA PLACONA. DELETION OF MICRORNA-22 ENHANCES THERMOGENIC GENE EXPRESSION IN WHITE ADIPOSE TISSUE OF OBESE MICE. FASEB JOURNAL, v. 32, n. 1, p. 2-pg., 2018-04-01. (17/01558-6, 15/21859-5)

LIMA, VANESSA M.; LINO, CAROLINE A.; SENGER, NATHALIA; SILVA, TABATHA DE OLIVEIRA; FONSECA, RENATA I. B.; BADER, MICHAEL; SANTOS, ROBSON A. S.; DONATO JUNIOR, JOSE; BARRETO-CHAVES, MARIA LUIZA M.; DINIZ, GABRIELA P.. Angiotensin II type 2 receptor mediates high fat diet-induced cardiomyocyte hypertrophy and hypercholesterolemia. Molecular and Cellular Endocrinology, v. 498, DEC 1 2019. (15/21859-5, 18/10338-2)