title: Adiponectin protects the genioglossus of rats against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.
abstract: BACKGROUND
  Obstructive sleep apnea hypopnea syndrome, characterized by chronic intermittent hypoxia (CIH), is closely correlated with genioglossus dysfunction. CIH has been identified to mediate mitochondrial damage in genioglossus. It has been reported that endoplasmic reticulum stress (ERS) could be induced by mitochondrial dysfunction. This study aimed to investigate the role of ERS in CIH-induced genioglossus injury, as well as the possible intervention effect of adiponectin (Ad) supplement in rats.
  
  
  METHODS
  Forty-five male Wistar rats were randomly divided into three groups and submitted to room air (group A, n=15) as a control or CIH (groups B and C, n=15, respectively). Throughout the exposure period, intravenous Ad was given in group C; while intravenous normal saline was simultaneously given in groups A and B. After 35-day exposure, genioglossus samples were obtained from the pentobarbital-anaesthetized rats via surgical dissection, following blood sampling. Western blotting was applied to detect expressions of ERS signals and associated apoptotic pathways in genioglossus. Serum adiponectin levels were assessed via enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Significant hypoadiponectinemia was revealed in group B only (P < 0.05). Compared to those in groups A and C, expressions of markers involved in ERS, such as glucose regulated protein 78 (GRP78), p-PERK, phosphorylated eukaryotic initiation factor 2a (p-eIF2a), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1a (p-IRE1a), spliced X-Box binding protein 1 (XBP1s) and activating transcription factor 6 (ATF6), were significantly enhanced in group B (all P < 0.01); while no significant difference was shown between groups A and C (all P > 0.05). ERSassociated apoptotic pathways were remarkably activated in group B. The involved markers detected as the expression of CCAAT/enhancer binding protein homologous protein (CHOP), B-cell lymphoma/leukemia associatied X protein (BAX) and caspase-12 were significantly elevated (all P < 0.01). Transvenous adiponectin supplement improved the above CIHinduced pathological changes in group C.
  
  
  CONCLUSIONS
  Beyond hypoadiponectinemia, CIH could enhance ERS and induce activation of ERS-associated apoptotic pathways in genioglossus, which could be significantly improved by adiponectin supplement.
authors.affiliation: Department of Respiratory Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhang
authors.forename: Han-Peng
authors.initials: HP
authors.lastname: Huang
authors.forename: Wen-Xiao
authors.initials: WX
authors.lastname: Ding
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.forename: Gan
authors.initials: G
authors.lastname: Lu
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Liu
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy
chemical_list: D052242:Adiponectin