title: Role of adipose tissue in methionine-choline-deficient model of non-alcoholic steatohepatitis (NASH).
abstract: Methionine-choline-deficient (MCD) diet is a widely used dietary model of non-alcoholic steatohepatitis (NASH) in rodents. However, the contribution of adipose tissue to MCD-induced steatosis, and inflammation as features of NASH are not fully understood. The goal of this study was to elucidate the role of adipose tissue fatty acid (FA) metabolism, adipogenesis, lipolysis, inflammation and subsequent changes in FA profiles in serum and liver in the pathogenesis of steatohepatitis. We therefore fed ob/ob mice with control or MCD diet for 5 weeks. MCD-feeding increased adipose triglyceride lipase and hormone sensitive lipase activities in all adipose depots which may be attributed to increased systemic FGF21 levels. The highest lipase enzyme activity was exhibited by visceral WAT. Non-esterified fatty acid (NEFA)-18:2n6 was the predominantly elevated FA species in serum and liver of MCD-fed ob/ob mice, while overall serum total fatty acid (TFA) composition was reduced. In contrast, an overall increase of all FA species from TFA pool was found in liver, reflecting the combined effects of increased FA flux to liver, decreased FA oxidation and decrease in lipase activity in liver. NAFLD activity score was increased in liver, while WAT showed no changes and BAT showed even reduced inflammation.
  
  
  CONCLUSIONS
  This study demonstrates a key role for adipose tissue lipases in the pathogenesis of NASH and provides a comprehensive lipidomic profiling of NEFA and TFA homeostasis in serum and liver. Our findings provide novel mechanistic insights for the role of WAT in progression of MCD-induced liver injury.
authors.affiliation: Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Pooja
authors.initials: P
authors.lastname: Jha
authors.affiliation: Core Facility for Mass Spectrometry, Medical University of Graz, Austria.
authors.forename: Astrid
authors.initials: A
authors.lastname: Knopf
authors.affiliation: Core Facility for Mass Spectrometry, Medical University of Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Koefeler
authors.affiliation: Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Carolin
authors.initials: C
authors.lastname: Lackner
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
authors.affiliation: Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Thierry
authors.initials: T
authors.lastname: Claudel
authors.affiliation: Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: michael.trauner@meduniwien.ac.at.
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002794:Choline / Q000378:metabolism*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D008066:Lipolysis / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008715:Methionine / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D008715:Methionine; D008049:Lipase; D002794:Choline
keywords: ATGL; FGF21; HSL; Lipolysis; Liver; NAFLD