title: Toll-like receptor 4 is critical for the development of resection-associated hepatic steatosis.
abstract: BACKGROUND
  A significant number of children with short bowel syndrome experience intestinal failure-associated liver disease. We recently demonstrated accelerated hepatic steatosis after 50% small bowel resection (SBR) in mice. Since SBR is associated with alterations in the gut microbiome, the purpose of this study was to determine whether TLR4 signaling is critical to the development of resection-associated hepatic steatosis.
  
  
  METHODS
  Male C57BL6 (control) and TLR4-knockout (KO) mice underwent 50% proximal SBR. Liver sections were analyzed to obtain the percent lipid content, and Ileal sections were assessed for morphological adaptation. Intestinal TLR4 mRNA expression was measured at 7days and 10weeks.
  
  
  RESULTS
  Compared to controls, TLR4 KO mice demonstrated similar weight gain and morphological adaptation after SBR. Hepatic steatosis was decreased 32-fold in the absence of TLR4. Intestinal TLR4 mRNA expression was significantly elevated 7days after SBR. We also found that TLR4 expression in the intestine was 20-fold higher in whole bowel sections compared with isolated enterocytes.
  
  
  CONCLUSIONS
  TLR4 signaling is critical for the development of resection-associated steatosis, but not involved in intestinal adaptation after massive SBR. Further studies are needed to delineate the mechanism for TLR4 signaling in the genesis of resection-associated liver injury.
  
  
  METHODS
  Animal study, not clinical.
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; St. Louis Children's Hospital, St. Louis, MO, USA.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Barron
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; St. Louis Children's Hospital, St. Louis, MO, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Bao
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; St. Louis Children's Hospital, St. Louis, MO, USA.
authors.forename: Bola G
authors.initials: BG
authors.lastname: Aladegbami
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; St. Louis Children's Hospital, St. Louis, MO, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Colasanti
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; St. Louis Children's Hospital, St. Louis, MO, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; St. Louis Children's Hospital, St. Louis, MO, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Erwin
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; St. Louis Children's Hospital, St. Louis, MO, USA. Electronic address: Brad.Warner@wustl.edu.
authors.forename: Brad W
authors.initials: BW
authors.lastname: Warner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012778:Short Bowel Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: IFALD; Short bowel syndrome; Steatosis; TLR4