期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 548, 期 -, 页码 196-203出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.01.038
关键词
Diabetic cardiomyopathy; EP4; Fatty acid metabolism; FOXO1; CD36
资金
- National Natural Science Foundation of China [81873474, 81570259, 81803527]
- Bureau of Education of Guangzhou Municipality [14CXY03]
- China postdoctoral science foundation [2019M662872]
EP4 deficiency in mice under high-fat diet resulted in cardiac hypertrophy and fibrosis, accompanied by reduced fatty acid uptake and inhibited ATP generation. EP4 tightly regulates the rates of cardiac fatty acid uptake and ATP generation via the FOXO1/CD36 signaling axis.
Background: Cardiac 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. Methods: Mice 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. Results: EP4(-/-) 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. Conclusion: EP4 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. (C) 2021 The Authors. Published by Elsevier Inc.
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