title: Chronic intermittent hypobaric hypoxia ameliorates endoplasmic reticulum stress mediated liver damage induced by fructose in rats.
abstract: OBJECTIVE
  High-fructose intake induces nonalcoholic fatty liver disease (NAFLD) and chronic intermittent hypobaric hypoxia (CIHH) has beneficial effects on the body. We hypothesized that CIHH has protective effects on the impaired hepar in fructose-fed rats.
  
  
  METHODS
  Sprague-Dawley rats (male, 160-180 g) were randomly divided into 4 groups: control group (CON), fructose group (FRUC, 10% fructose in drinking water for 6 weeks), CIHH group (simulated 5000m altitude, 6h per day for 6 weeks), and CIHH plus fructose groups (CIHH-F). Histopathology of liver, arterial blood pressure, blood biochemicals, hepatocyte apoptosis, and marker proteins of endoplasmic reticulum stress (ERS) were measured.
  
  
  RESULTS
  The arterial blood pressure, body mass index, abdominal fat weight and liver weight were increased in FRUC rats but not in CIHH-F rats. Likewise, the serum glucose, insulin, insulin C peptide, triglyceride (TG) and total cholesterol (TC) were elevated in FRUC rats but not in CIHH-F rats after fasting 12h. Meanwhile, the hepatic steatosis and hepatocyte apoptosis occurred in FRUC rats but not in CIHH-F rats. Finally the expression of ERS markers including GRP78 (glucose-regulated protein78), CHOP (C/EBP Homologous Protein), and caspase-12 in hepatic tissue were up-regulated in FRUC rats, but such up-regulation was not observed in CIHH-F rats.
  
  
  CONCLUSIONS
  Our results suggest that CIHH protect hepar against hepatic damage through inhibition of ERS in fructose-fed rats. CIHH might be the new therapy for NAFLD.
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang, China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Laboratory Animal, Hebei Medical University, Shijiazhuang, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Teng
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang, China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang, China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, China. Electronic address: zhyhenry@hotmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang, China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, China. Electronic address: wangsheng@hebmu.edu.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000399:Air Pressure; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D062186:Arterial Pressure; D001794:Blood Pressure; D015992:Body Mass Index; D053148:Caspase 3 / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005632:Fructose / Q000633:toxicity*; D000860:Hypoxia; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013549:Sweetening Agents / Q000633:toxicity*
chemical_list: D013549:Sweetening Agents; D005632:Fructose; D053148:Caspase 3
keywords: Apoptosis; Chronic intermittent hypobaric hypoxia; Endoplasmic reticulum stress; Fructose (PubChem CID: 5984); Hepar; Metabolic syndrome