Prostaglandin E receptor subtype 4 protects against diabetic cardiomyopathy by modulating cardiac fatty acid metabolism via FOXO1/CD36 signalling
Prostaglandin E receptor subtype 4 protects against diabetic cardiomyopathy by modulating cardiac fatty acid metabolism via FOXO1/CD36 signalling
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前列腺素 E 受体亚型 4 通过 FOXO1/CD36 信号传导调节心脏脂肪酸代谢，预防糖尿病心肌病
DOI：
10.1016/j.bbrc.2021.01.038
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发表时间：
2021
影响因子：
3.1
通讯作者：
Liu Shiming
中科院分区：
文献类型：
--
作者：
Ying Fan;Liu Hao;Tang Eva Hoi Ching;Lakhani Ishan;Liu Ningning;Xia Zhengyuan;Liu Shiming
背景心脏脂肪酸代谢对于维持正常的心脏功能和应对各种疾病应激（如糖尿病）至关重要。EP 4在心肌细胞中广泛表达，并已被证明在心脏功能中发挥作用。然而，它在调节心脏脂肪酸代谢的功能仍然未知。本研究观察了EP 4缺乏对心功能、心肌细胞肥大和心肌纤维化的影响。结果EP 4 −/−小鼠心肌向心性肥大，FOXO 1/CD 36信号通路介导的ATP生成抑制和脂肪酸摄取减少导致心肌纤维化。结论EP 4通过FOXO 1/CD 36信号通路调节心肌细胞脂肪酸摄取和ATP生成。我们的研究为EP 4与心脏脂肪酸转运之间的联系提供了证据，并进一步指出EP 4可能是调节脂肪酸代谢和抑制糖尿病后心脏组织特异性功能损害的潜在靶点。
BackgroundCardiac fatty acid metabolism is essential for maintaining normal cardiac function at baseline and in response to various disease stress, like diabetes. EP4 is widely expressed in cardiomyocytes and has been demonstrated to play a role in cardio function. However, its function in regulating cardiac fatty acid metabolism is remained unknown.MethodsMice were fed with standard chow or high-fat for eight weeks. The effects of EP4 deficiency on cardiac function, cardiomyocytes hypertrophy and myocardial fibrosis were studied. The possible regulatory mechanisms were further investigated.ResultsEP4−/−mice exhibited concentric hypertrophy and myocardial fibrosis with cardiac energy deprivation due to reduction of fatty acid uptake and inhibition of ATP generation mediated by FOXO1/CD36 signalling. Moreover, pharmacologically activated EP4 alleviated impaired fatty acid transport and insufficient ATP generation in cardiomyocytes.ConclusionEP4 tightly coordinates the rates of cardiac fatty acid uptake and ATP generation via FOXO1/CD36 signalling axis. Our study provides evidences for the link between EP4 and cardiac fatty acid transport and further pointed out that EP4 could be a potential target for modulating fatty acid metabolism and curbing cardiac tissue-specific impairment of function following diabetes.