Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Hypertension Unit, Heart Institute, University of Sao Paulo, Sao Paulo, Brazil.
Exp Physiol. 2022 Aug;107(8):892-905. doi: 10.1113/EP090315. Epub 2022 Jul 13.
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.
本研究的核心问题是什么？肥胖诱导的饮食如何影响参与雌性小鼠心脏肥大的 microRNAs（miRNAs）的表达？主要发现及其重要性是什么？喂食肥胖诱导饮食的雌性小鼠表现出与 miRNA-143-3p 水平升高、Sox6mRNA 水平降低和 Myh7mRNA 水平升高相关的心脏肥大。抑制 miRNA-143-3p 增加了心肌细胞中 Sox6mRNA 水平并降低了 Myh7 表达，并防止了血管紧张素 II 诱导的心肌细胞肥大。结果表明，miRNA-143-3p-Sox6-Myh7 通路可能在肥胖诱导的心脏肥大中发挥关键作用。
肥胖会引起与死亡率升高相关的心脏代谢紊乱。我们之前已经表明，在雄性小鼠的肥胖诱导性心脏肥大中，miRNA（miRNA）表达谱发生了改变。在这里，我们研究了肥胖诱导的饮食对雌性小鼠心脏肥大相关 miRNA 表达的影响。喂食肥胖诱导饮食的雌性小鼠体重增加、葡萄糖耐量受损、胰岛素抵抗和血脂异常。此外，肥胖的雌性小鼠表现出与几种 miRNAs 水平升高相关的心脏肥大，包括 miR-143-3p。生物信息学分析确定 Sox6（Myh7 基因转录的调节因子）为 miR-143-3p 的预测靶标。喂食肥胖诱导饮食的雌性小鼠的 Sox6mRNA 水平降低，心脏中的 Myh7 表达增加。心肌细胞中的功能丧失研究表明，抑制 miR-143-3p 增加了 Sox6mRNA 水平并降低了 Myh7 表达。总之，我们的研究结果表明，雌性小鼠与肥胖相关的心脏肥大伴随着多种 miRNAs 的改变，并表明 miR-143-3p-Sox6-Myh7 通路可能在肥胖诱导的心脏肥大中发挥关键作用。
