The miRNA-143-3p-Sox6-Myh7 pathway is altered in obesogenic diet-induced cardiac hypertrophy

Author(s):Show less -

de Oliveira Silva, Tabatha ; Lino, Caroline A. ; Miranda, Juliane B. ; Balbino-Silva, Camila S. ; Lunardon, Guilherme ; Lima, Vanessa M. ; Jensen, Leonardo ; Donato, Jose, Jr. ; Irigoyen, Maria Claudia ; Barreto-Chaves, Maria Luiza M. ; Diniz, Gabriela P.

• Document type: Journal article
• Source: Experimental Physiology; v. 107, n. 8, p. 14-pg., 2022-07-13.

Abstract

New Findings What is the central question of this study? What is the effect of an obesogenic diet on the expression of microRNAs (miRNAs) involved in cardiac hypertrophy in female mice? What is the main finding and its importance? Female mice fed an obesogenic diet exhibited cardiac hypertrophy associated with increased levels of miRNA-143-3p, decreased mRNA levels of Sox6 and increased mRNA levels of Myh7. Inhibition of miRNA-143-3p increased Sox6 mRNA levels and reduced Myh7 expression in cardiomyocytes, and prevented angiotensin II-induced cardiomyocyte hypertrophy. The results indicate that the miRNA-143-3p-Sox6-Myh7 pathway may play a key role in obesity-induced cardiac hypertrophy. Obesity induces cardiometabolic disorders associated with a high risk of mortality. We have previously shown that the microRNA (miRNA) expression profile is changed in obesity-induced cardiac hypertrophy in male mice. Here, we investigated the effect of an obesogenic diet on the expression of miRNAs involved in cardiac hypertrophy in female mice. Female mice fed an obesogenic diet displayed an increased body weight gain, glucose intolerance, insulin resistance and dyslipidaemia. In addition, obese female mice exhibited cardiac hypertrophy associated with increased levels of several miRNAs, including miR-143-3p. Bioinformatic analysis identified Sox6, regulator of Myh7 gene transcription, as a predicted target of miR-143-3p. Female mice fed an obesogenic diet exhibited decreased mRNA levels of Sox6 and increased expression of Myh7 in the heart. Loss-of-function studies in cardiomyocytes revealed that inhibition of miR-143-3p increased Sox6 mRNA levels and reduced Myh7 expression. Collectively, our results indicate that obesity-associated cardiac hypertrophy in female mice is accompanied by alterations in diverse miRNAs, and suggest that the miR-143-3p-Sox6-Myh7 pathway may play a key role in obesity-induced cardiac hypertrophy. (AU)

• FAPESP's process: 18/10338-2 - Role of microRNA-22 in differentiation of brown adipocytes and in browning of white adipose tissue
• Grantee: Gabriela Placoná Diniz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/21491-6 - Impact of miRNA-22 and cell senescence in metabolic dysfunctions induced by obesity
• Grantee: Caroline Antunes Lino
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/26657-0 - Impact of miRNA-22 in the vascular reactivity of obese mice
• Grantee: Camila Stephanie Balbino Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/25814-4 - Analysis of the role of lysine methyltransferase SETD7 in metabolic and cardiovascular changes induced by obesity in females
• Grantee: Juliane Braga Miranda
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/01558-6 - Role of microRNA-22 in the adipogenesis and in the browning process of adipose tissue in obesity induced by high-fat diet
• Grantee: Vanessa Morais Lima
• Support Opportunities: Scholarships in Brazil - Post-Doctoral