NAFLD Phosphoproteomics: A Functional Piece of the Precision Puzzle.

Wattacheril J, Rose KL, Hill S et al.

Center for Liver Disease and Transplantation, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, United States of America.

Hepatology research : the official journal of the Japan Society of Hepatology. Mar 2017.

Molecular signaling events associated with the necroinflammatory changes in nonalcoholic steatohepatitis are not well understood. 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 NAFLD. Class III obese subjects undergoing bariatric surgery underwent liver biopsy (8 NOR, 8 simple steatosis and 8 NASH). Our strategy was unbiased, comparing global differences in liver protein reversible phosphorylation events across the 24 subjects. Of the 3,078 phosphorylation sites assigned (2,465 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). Statistical analyses of canonical signaling pathways identified carbohydrate metabolism and RNA post-transcriptional modification among the most over-represented networks. 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. Pubmed

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