title: Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model.
abstract: OBJECTIVE
  The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD.
  
  
  METHODS
  Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts.
  
  
  RESULTS
  Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts.
  
  
  CONCLUSIONS
  Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD.
authors.affiliation: Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. lee.gorden@vanderbilt.edu
authors.forename: D Lee
authors.initials: DL
authors.lastname: Gorden
authors.forename: Pavlina T
authors.initials: PT
authors.lastname: Ivanova
authors.forename: David S
authors.initials: DS
authors.lastname: Myers
authors.forename: J Oliver
authors.initials: JO
authors.lastname: McIntyre
authors.forename: Michael N
authors.initials: MN
authors.lastname: VanSaun
authors.forename: J Kelly
authors.initials: JK
authors.lastname: Wright
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Matrisian
authors.forename: H Alex
authors.initials: HA
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D004075:Diglycerides / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020404:Glycerophospholipids / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D013045:Species Specificity; D055815:Young Adult
chemical_list: D004075:Diglycerides; D020404:Glycerophospholipids; D008055:Lipids