Spexin protects cardiomyocytes from hypoxia-induced metabolic and mitochondrial dysfunction
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Spexin (SPX) is a novel peptide with pleiotropic functions in adipose tissue including energy balance adjustment, fatty acid uptake, and glucose homeostasis. SPX level is closely associated with cardiovascular risk factors such as age, obesity, hypertension, and diabetes; however, its physiological significance in the cardiovascular system remains mostly undefined. We therefore here investigated the roles of SPX in regulating hypoxia-induced alterations in energy metabolism and mitochondrial function. We firstly confirmed that SPX is expressed in human and mouse cardiac tissue and documented that exposure to hypoxia in vitro reduces SPX level in rat H9C2 cardiomyocytes and primary neonatal rat ventricular myocytes (NRVMs). We then treated primary NRVMs with SPX before exposure to hypoxia, which (1) promoted fatty acid metabolism by enhancing expression of FAT/CD36, CPT1, ACADM, and PPAR-a and PGC1-a; (2) did not improve impaired glucose uptake; and (3) significantly prevented the downregulation of TFAM and mitochondrial electron transport chain complex and restrained UCP2 level and reactive oxygen species (ROS) production, thus enhancing ATP level in cardiomyocytes. In summary, SPX protects energy and mitochondrial homeostasis of cardiomyocytes during hypoxia, thereby highlighting the potential importance of SPX in the treatment of cardiovascular diseases.
KeywordsSpexin Hypoxia Fatty acid metabolism mitochondrial function
YL and LS conducted the experiments, analyzed the data, and supervised and wrote the manuscript; LQZ participated equally in the first authorship and conducted experiments, drafted the figure, and analyzed the data and co-wrote the manuscript; MQS, HL, YW, and YKW conducted the experiments and analyzed the data; DL, CGD and CYZ performed the experimental approaches and data to the work; YTG co-wrote the manuscript and revised it for critically important intellectual content; YL* helped to identify and formulate the research and interpreted the experiments. All the authors approved the final version of the manuscript.
This work was supported by the Key Program of the National Natural Science Foundation of China (81830012), General Program of the National Natural Science Foundation of China (81670297, 81800332), and Doctoral Fund of Ministry of Education of Heilongjiang Province (LBH-Z17180).
Compliance with ethical standards
All patients recruited into the study signed written informed consent and the study complied with the principles that govern the use of human tissues outlined in the Declaration of Helsinki. Left atrial appendages were obtained as surgical specimens from patients undergoing cardiac surgery for mitral valve replacement, following established procedures approved by Ethic Committee of the Harbin Medical University. The specimens were stored in liquid nitrogen immediately and transported to laboratory
Conflict of interest
The authors declare that they have no conflicts of interest.
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