Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction

• Main Authors: Yuan Liu, Li-Na Li, Sen Guo, Xiao-Yan Zhao, Yu-Zhou Liu, Cui Liang, Sheng Tu, Dan Wang, Ling Li, Jian-Zeng Dong, Lu Gao, Hai-Bo Yang
• Format: Article
• Language: English
• Published: Elsevier 2018-09-01
• Series: Redox Biology
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213231718304774

Melatonin has been shown to inhibit myocardial infarction-induced apoptosis, its function in heart failure with preserved ejection fraction (HFpEF) has not been investigated. This study aimed to investigate whether melatonin attenuates obesity-related HFpEF. Male mice were fed a high-fat diet (HFD) from weaning to 6 months of age to induce HFpEF. The mice were orally administered melatonin (50 mg/kg) by 3 weeks. Diastolic function was significantly improved by melatonin supplementation in mice fed an HFD. Melatonin attenuated obesity-induced myocardial oxidative stress and apoptosis and promoted the secretion of C1q/tumour necrosis factor-related protein 3 (CTRP3) by adipose tissue. And depletion of circulating CTRP3 largely abolished melatonin-mediated cardio-protection. Melatonin-mediated secretion of adipocyte-derived CTRP3 activated NF-E2-related factor 2 (Nrf2), which were largely abrogated by knocking down CTRP3 in adipocytes or Nrf2 in cardiomyocytes. Nrf2 activation was mediated by miR-200a, and a miR-200a antagomir offset the effects of melatonin-conditioned medium on Nrf2 expression. Our results indicate that melatonin can be used to treat and prevent obesity-related HFpEF. Keywords: Melatonin, HFpEF, CTRP3, Adipocyte, Oxidative stress, Apoptosis