In this video, Tábatha de Oliveira Silva PhD student at the Institute of Biomedical Sciences of the University of Sao Paulo in Brazil, discusses her group's recent paper on the biological mechanisms involved in cardiovascular dysfunctions related to obesity. Read more in Experimental Physiology https://physoc.onlinelibrary.wiley.com/doi/10.1113/EP090315 The miRNA-143-3p–Sox6–Myh7 pathway is altered in obesogenic diet-induced cardiac hypertrophy Tábatha de Oliveira Silva,Caroline A. Lino,Juliane B. Miranda,Camila S. Balbino-Silva,Guilherme Lunardon,Vanessa M. Lima,Leonardo Jensen,Jose Donato Jr,Maria Cláudia Irigoyen,Maria Luiza M. Barreto-Chaves,Gabriela P. Diniz 107(8), pp. 892-905 Transcript: Hello everyone! My name is Tábatha. I am doing a PhD at the Institute of Biomedical Sciences of the University of Sao Paulo in Brazil, under the supervision of Professor Gabriela Diniz. In the last years, our research group has investigated the biological mechanisms involved in cardiovascular dysfunctions related to obesity. MicroRNAs (miRNAs), which are small non-coding RNAs that may affect the expression of mRNAs, have been implicated in diverse cardiovascular disorders. Recently, we published an article in Experimental Physiology, in which we investigated the effect of an obesogenic diet on the expression of miRNAs involved in cardiac hypertrophy in female mice. To address this question, female mice were fed an obesogenic diet to induce obesity. We found that female mice fed an obesogenic diet had an increased body weight gain, glucose intolerance, insulin resistance, and dyslipidemia. In addition, obese female mice exhibited compromised diastolic function and cardiac hypertrophy, which were accompanied by alterations in diverse miRNAs. Moreover, we found that miR-143-3p was one of the most upregulated miRNAs in response to an obesogenic diet. One of the predicted targets of miR-143-3p is Sox6, a transcriptional factor that inhibits Myh7 transcription. Myh7 is a low ATPase-activity myosin increased in several pathological cardiac hypertrophy models. (FIG 6) Interestingly, we found that the higher levels of miR-143-3p in the heart of obese female mice were accompanied by reduced Sox6 expression and increased Myh7 expression. To investigate whether the increased miR-143-3p levels found in the heart of obese female mice could be involved in the reduction of Sox6 expression and the increase of Myh7 expression, we used a loss-of-function approach in cardiomyocyte cultures. We found that a miR-143-3p inhibitor increased Sox6 expression and reduced Myh7 expression in cardiomyocytes, suggesting that miR-143-3p increases Myh7 expression by suppressing of Sox6. Together, our results suggest that the miR-143-3p-Sox6-Myh7 pathway may play a key role in obesity-induced cardiac hypertrophy. Thank you!

• published: 01 Sep 2022
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