title: Non-alcoholic fatty liver disease phosphoproteomics: A functional piece of the precision puzzle.
abstract: BACKGROUND
  Molecular signaling events associated with the necroinflammatory changes in nonalcoholic steatohepatitis (NASH) are not well understood.
  
  
  OBJECTIVE
  To understand the molecular basis of NASH, we evaluated reversible phosphorylation events in hepatic tissue derived from Class III obese subjects by phosphoproteomic means with the aim of highlighting key regulatory pathways that distinguish NASH from non-alcoholic fatty liver disease (also known as simple steatosis; SS).
  
  
  METHODS
  Class III obese subjects undergoing bariatric surgery underwent liver biopsy (eight normal patients, eight with simple steatosis, and eight NASH patients). Our strategy was unbiased, comparing global differences in liver protein reversible phosphorylation events across the 24 subjects.
  
  
  RESULTS
  Of the 3078 phosphorylation sites assigned (2465 phosphoserine, 445 phosphothreonine, 165 phosphotyrosine), 53 were altered by a factor of 2 among cohorts, and of those, 12 were significantly increased or decreased by ANOVA (P < 0.05).
  
  
  CONCLUSIONS
  Statistical analyses of canonical signaling pathways identified carbohydrate metabolism and RNA post-transcriptional modification among the most over-represented networks.
  
  
  CONCLUSIONS
  Collectively, these results raise the possibility of abnormalities in carbohydrate metabolism as an important trigger for the development of NASH, in parallel with already established abnormalities in lipid metabolism.
authors.affiliation: Center for Liver Disease and Transplantation, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Wattacheril
authors.affiliation: Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Rose
authors.affiliation: Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Salisha
authors.initials: S
authors.lastname: Hill
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Lanciault
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Clark R
authors.initials: CR
authors.lastname: Murray
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Kay
authors.initials: K
authors.lastname: Washington
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Williams
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: English
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Spann
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Clements
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Naji
authors.initials: N
authors.lastname: Abumrad
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Charles Robb
authors.initials: CR
authors.lastname: Flynn
keywords: non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; pathway analysis; phosphoproteomics; phosphorylation; proteomics; simple steatosis