title: Fenofibrate does not affect burn-induced hepatic endoplasmic reticulum stress.
abstract: BACKGROUND
  Burn injury causes major metabolic derangements such as hypermetabolism, hyperlipidemia, and insulin resistance and is associated with liver damage, hepatomegaly, and hepatic endoplasmic reticulum (ER) stress. Although the physiological consequences of such derangements have been delineated, the underlying molecular mechanisms remain unknown. Previously, it was shown that fenofibrate improves patient outcome by attenuating postburn stress responses.
  
  
  METHODS
  Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, regulates liver lipid metabolism and has been used to treat hypertriglyceridemia and hypercholesterolemia for many years. The aim of the present study is to determine the effects of fenofibrate on burn-induced hepatic morphologic and metabolic changes. We randomized rats to sham, burn injury, and burn injury plus fenofibrate. Animals were sacrificed and livers were assessed at 24 or 48 h post burn.
  
  
  RESULTS
  Burn injury decreased albumin and increased alanine transaminase (P = 0.1 versus sham), indicating liver injury. Fenofibrate administration did not restore albumin or decrease alanine transaminase. In addition, ER stress was significantly increased after burn injury both with and without fenofibrate (P < 0.05 versus sham). Burn injury increased fatty acid metabolism gene expression (P < 0.05 versus sham), downstream of peroxisome proliferator-activated receptor alpha. Fenofibrate treatment increased fatty acid metabolism further, which reduced postburn hepatic steatosis (burn versus sham P < 0.05, burn + fenofibrate versus sham not significant).
  
  
  CONCLUSIONS
  Fenofibrate did not alleviate thermal injury-induced hepatic ER stress and dysfunction, but it reduced hepatic steatosis by modulating hepatic genes related to fat metabolism.
authors.affiliation: Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Yaeko
authors.initials: Y
authors.lastname: Hiyama
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Marshall
authors.forename: Robert
authors.initials: R
authors.lastname: Kraft
authors.forename: Anna
authors.initials: A
authors.lastname: Arno
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D006529:Hepatomegaly / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D050155:Lipogenesis / Q000187:drug effects; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D000960:Hypolipidemic Agents; D014280:Triglycerides; D011345:Fenofibrate
keywords: Apoptosis; Burn; Endoplasmic reticulum stress; Fenofibrate; Liver metabolism; Steatosis