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

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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.

• Tipo de documento: Artigo Científico
• Fonte: Experimental Physiology; v. 107, n. 8, p. 14-pg., 2022-07-13.

Resumo

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)

• Processo FAPESP: 18/10338-2 - Impacto do microRNA-22 na diferenciação de adipócitos marrons e no processo de browning do tecido adiposo branco
• Beneficiário: Gabriela Placoná Diniz
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/21491-6 - Impacto do miRNA-22 e da senescência celular nas disfunções metabólicas induzidas pela obesidade
• Beneficiário: Caroline Antunes Lino
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/26657-0 - Impacto do miRNA-22 na reatividade vascular de camundongos obesos
• Beneficiário: Camila Stephanie Balbino Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 18/25814-4 - Análise do papel da lisina metiltransferase SETD7 nas alterações metabólicas e cardiovasculares induzidas pela obesidade em fêmeas
• Beneficiário: Juliane Braga Miranda
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/01558-6 - Papel do microRNA-22 na adipogênese e processo de browning do tecido adiposo na obesidade induzida pela dieta rica em gordura
• Beneficiário: Vanessa Morais Lima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado