title: Adiponectin partially rescues high glucose/high fat-induced impairment of mitochondrial biogenesis and function in a PGC-1α dependent manner.
abstract: 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.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xian, China. lingtao@fmmu.edu.cn.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: W-J
authors.initials: WJ
authors.lastname: Yan
authors.forename: J-L
authors.initials: JL
authors.lastname: Zhang
authors.forename: F-Y
authors.initials: FY
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Gao
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Bond Law
authors.forename: L
authors.initials: L
authors.lastname: Tao
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005947:Glucose / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D051381:Rats
chemical_list: D052242:Adiponectin; D003470:Culture Media; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D005947:Glucose