title: Lipidomic analysis of the liver identifies changes of major and minor lipid species in adiponectin deficient mice.
abstract: Adiponectin protects from hepatic fat storage but adiponectin deficient mice (APN-/-) fed a standard chow do not develop liver steatosis. This indicates that other pathways might be activated to compensate for adiponectin deficiency. An unbiased and comprehensive screen was performed to identify hepatic alterations of lipid classes in these mice. APN-/- mice had decreased hepatic cholesteryl esters while active SREBP2 and systemic total cholesterol were not altered. Upregulation of cytochromes for bile acid synthesis suggests enhanced biliary cholesterol excretion. Analysis of 37 individual fatty acid species showed reduced stearate whereas total fatty acids were not altered. Total amount of triglycerides and phospholipids were equally abundant. A selective increase of monounsaturated phosphatidylcholine and phosphatidylethanolamine which positively correlate with hepatic and systemic triglycerides with the latter being elevated in APN-/- mice, was identified. Stearoyl-CoA desaturase 1 (SCD1) is involved in the synthesis of monounsaturated fatty acids and despite higher mRNA expression enzyme activity was not enhanced. Glucosylceramide postulated to contribute to liver damage was decreased. This study demonstrates that adiponectin deficiency is associated with hepatic changes in lipid classes in mice fed a standard chow which may protect from liver steatosis.
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Wanninger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bauer
authors.forename: Kristina
authors.initials: K
authors.lastname: Eisinger
authors.forename: Markus
authors.initials: M
authors.lastname: Neumeier
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Christa
authors.initials: C
authors.lastname: Buechler
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism; D005963:Glucosylceramides / Q000378:metabolism; D050356:Lipid Metabolism; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; D001647:Bile Acids and Salts; D002788:Cholesterol Esters; D003580:Cytochromes; D004041:Dietary Fats; D005227:Fatty Acids; D005963:Glucosylceramides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2; D014280:Triglycerides; C483858:phosphatidylethanolamine; D002784:Cholesterol; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase