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

作者：Liu, Yuan; Li, Li-Na; Guo, Sen; Zhao, Xiao-Yan; Liu, Yu-Zhou; Liang, Cui; Tu, Sheng; Wang, Dan; Li, Ling; Dong, Jian-Zeng; Gao, Lu^*; Yang, Hai-Bo^*

来源：Redox Biology, 2018, 18: 211-221.

DOI：10.1016/j.redox.2018.07.007

• Melatonin
• HFpEF
• CTRP3
• Adipocyte
• Oxidative stress
• Apoptosis

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.

• 出版日期2018-9
• 单位郑州大学