Spexin protects cardiomyocytes from hypoxia-induced metabolic and mitochondrial dysfunction
Spexin protects cardiomyocytes from hypoxia-induced metabolic and mitochondrial dysfunction
复制标题
Spexin 保护心肌细胞免受缺氧引起的代谢和线粒体功能障碍
DOI：
10.1007/s00210-019-01708-0
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发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Li, Yue
中科院分区：
文献类型：
--
作者：
Liu, Yang;Sun, Li;Li, Yue
Spexin（SPX）是一种新型的脂肪多肽，在脂肪组织中具有调节能量平衡、脂肪酸摄取和葡萄糖稳态等多种功能。SPX水平与心血管危险因素如年龄、肥胖、高血压和糖尿病密切相关;然而，其在心血管系统中的生理意义仍然大多不明确。因此，我们在这里调查的作用，SPX在调节缺氧引起的能量代谢和线粒体功能的改变。我们首次证实了SPX在人和小鼠心脏组织中表达，并记录了体外暴露于缺氧降低大鼠H9 C2心肌细胞和原代新生大鼠心室肌细胞（NRVM）中的SPX水平。结果表明：（1）SPX可通过增强FAT/CD 36、CPT 1、ACADM、PPAR-a和PGC 1-a的表达，促进脂肪酸代谢，但对糖代谢异常无明显改善作用;显著抑制TFAM和线粒体电子传递链复合物的下调，抑制UCP 2水平和活性氧（ROS）的产生，从而提高心肌细胞中的ATP水平。总之，SPX在缺氧期间保护心肌细胞的能量和线粒体稳态，从而突出了SPX在心血管疾病治疗中的潜在重要性。
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.