title: Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response.
abstract: Hemorrhagic shock is a leading cause of trauma-related mortality in both civilian and military settings. Resuscitation often results in reperfusion injury and survivors are susceptible to developing multiple organ failure (MOF). The impact of fed state on the overall response to shock and resuscitation has been explored in some murine models but few clinically relevant large animal models. We have previously used metabolomics to establish that the fed state results in a different metabolic response in the porcine liver following hemorrhagic shock and resuscitation. In this study, we used our clinically relevant model of hemorrhagic shock and polytrauma and the Illumina HiSeq platform to determine if the liver transcriptomic response is also altered with respect to fed state. Functional analysis of the response to shock and resuscitation confirmed several typical responses including carbohydrate metabolism, cytokine inflammation, decreased cholesterol synthesis, and apoptosis. Our findings also suggest that the fasting state, relative to a carbohydrate prefed state, displays decreased carbohydrate metabolism, increased cytoskeleton reorganization and decreased inflammation in response to hemorrhagic shock and reperfusion. Evidence suggests that this is a consequence of a shrunken, catabolic state of the liver cells which provides an anti-inflammatory condition that partially mitigates hepatocellar damage.
authors.affiliation: Department of Surgery, Division of Critical Care and Acute Care Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Determan
authors.affiliation: Department of Surgery, Division of Critical Care and Acute Care Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Department of Surgery, Division of Critical Care and Acute Care Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Aaron
authors.initials: A
authors.lastname: Becker
authors.affiliation: Department of Surgery, Division of Critical Care and Acute Care Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Witowski
authors.affiliation: Department of Surgery, Division of Critical Care and Acute Care Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lusczek
authors.affiliation: Department of Surgery, Division of Critical Care and Acute Care Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Kristine
authors.initials: K
authors.lastname: Mulier
authors.affiliation: Department of Surgery, Division of Critical Care and Acute Care Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Beilman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D050260:Carbohydrate Metabolism / Q000235:genetics; D002784:Cholesterol / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009104:Multiple Trauma / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D009752:Nutritional Status; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D034421:Sus scrofa; D059467:Transcriptome / Q000502:physiology*
chemical_list: D016207:Cytokines; D002784:Cholesterol