Wang H, Yan W-J, Zhang J-L, Zhang F-Y, Gao C, Wang Y-J, Bond Law W, Tao L
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xian, China.
Eur Rev Med Pharmacol Sci. 2017 Jan;21(3):590-599.
Plasma adiponectin (APN) levels are decreased in diabetic patients. Dysfunctional mitochondrial biogenesis is involved in type 2 diabetes (T2DM) pathogenesis, by unclear mechanisms. The present study determined (1) whether myocardial mitochondrial biogenesis was impaired in cardiomyocytes exposed to a high glucose/high fat (HGHF) medium (a T2DM in vitro model), (2) the effects of APN administration upon mitochondrial biogenesis in cardiomyocytes affected by HGHF incubation, and 3) the involved underlying mechanisms.
Neonatal rat ventricular myocytes (NRVMs) were isolated and incubated in HGHF medium. Mitochondrial function was assessed by ATP content, and fluorescent microscopic analysis of myocardial apoptosis was determined by TUNEL staining and caspase-3 activity.
HGHF treatment reduced mitochondrial biogenesis, altered mitochondrial structure, and induced mitochondrial dysfunction in NRVMs. Administration of APN partially rescued these effects. However, siRNA-mediated knockdown of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) significantly blocked the beneficial effects of APN in mitochondria and cardiomyocytes subjected to hypoxia/reoxygenation injury.
In the current study, we have provided the direct in vitro evidence that APN partially rescues HGHF-induced impairment of mitochondrial biogenesis and function via PGC-1α-mediated signaling.
糖尿病患者血浆脂联素（APN）水平降低。线粒体生物合成功能障碍参与2型糖尿病（T2DM）发病机制，但其机制尚不清楚。本研究旨在确定：（1）在暴露于高糖/高脂（HGHF）培养基（一种T2DM体外模型）的心肌细胞中，心肌线粒体生物合成是否受损；（2）给予APN对受HGHF孵育影响的心肌细胞中线粒体生物合成的作用；（3）相关的潜在机制。
分离新生大鼠心室肌细胞（NRVMs）并在HGHF培养基中孵育。通过ATP含量评估线粒体功能，通过TUNEL染色和caspase-3活性测定心肌细胞凋亡的荧光显微镜分析。
HGHF处理降低了NRVMs中的线粒体生物合成，改变了线粒体结构，并诱导了线粒体功能障碍。给予APN可部分挽救这些效应。然而，小干扰RNA介导的过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）敲低显著阻断了APN对缺氧/复氧损伤的线粒体和心肌细胞的有益作用。
在本研究中，我们提供了直接的体外证据，表明APN通过PGC-1α介导的信号通路部分挽救HGHF诱导的线粒体生物合成和功能损伤。
