title: BH3-only proteins contribute to steatotic liver ischemia-reperfusion injury.
abstract: BACKGROUND
  Ischemia-reperfusion injury (IRI) to the liver continues to be a source of significant morbidity, especially in patients with hepatic steatosis. This is a growing problem given the increase in nonalcoholic fatty liver disease. B-cell lymphoma-2 homology3-only members of the B-cell lymphoma-2 protein family are known mediators of cellular apoptosis, although their role in hepatic IRI is still emerging. The goal of this study was to investigate the effect of Bim and Bid on warm hepatic IRI in the setting of steatosis.
  
  
  METHODS
  Lean and obese Bim and/or Bid wild-type (WT) and double knockout (DKO) mice underwent 60 min of warm hepatic ischemia using a 70% segmental occlusion technique. Obesity and hepatic steatosis were induced using a high fat diet. Hepatocellular injury patterns were compared among lean and steatotic mice after reperfusion. Differences were analyzed using a Student t-test and reported as mean ± standard error of the mean.
  
  
  RESULTS
  DKO mice were protected from IRI relative to WT. A high fat diet created equal degrees of steatosis in both WT and DKO mice. The IRI was increased in steatotic WT livers; however, DKO mice remained protected relative to WT despite hepatic steatosis.
  
  
  CONCLUSIONS
  The B-cell lymphoma-2 homology3-only proteins are important mediators of hepatic IRI in both lean and steatotic livers. These mechanisms have been underappreciated in steatotic liver injury and may be leveraged as targets for intervention in clinical scenarios such as transplant and hypovolemic shock.
authors.affiliation: Department of Surgery, Washington University, Saint Louis, Missouri.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: DuBray
authors.affiliation: Department of Surgery, Washington University, Saint Louis, Missouri.
authors.forename: Kendra D
authors.initials: KD
authors.lastname: Conzen
authors.affiliation: Department of Surgery, Washington University, Saint Louis, Missouri.
authors.forename: Gundumi A
authors.initials: GA
authors.lastname: Upadhya
authors.affiliation: Department of Surgery, Washington University, Saint Louis, Missouri.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Gunter
authors.affiliation: Department of Surgery, Washington University, Saint Louis, Missouri.
authors.forename: Jianluo
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Surgery, Washington University, Saint Louis, Missouri.
authors.forename: Brett L
authors.initials: BL
authors.lastname: Knolhoff
authors.affiliation: Department of Surgery, Washington University, Saint Louis, Missouri.
authors.forename: Thallachallour
authors.initials: T
authors.lastname: Mohanakumar
authors.affiliation: Department of Surgery, Washington University, Saint Louis, Missouri.
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
authors.affiliation: Department of Surgery, University of Mississippi Medical Center, Jackson, Mississippi. Electronic address: cdanderson@umc.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Anderson
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D005234:Fatty Liver / Q000150:complications* / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C494815:Bid protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins
keywords: Apoptosis; BCL-2 proteins; Ischemia–reperfusion; Steatosis