title: Akt2 is required for hepatic lipid accumulation in models of insulin resistance.
abstract: Insulin drives the global anabolic response to nutrient ingestion, regulating both carbohydrate and lipid metabolism. Previous studies have demonstrated that Akt2/protein kinase B is critical to insulin's control of glucose metabolism, but its role in lipid metabolism has remained controversial. Here, we show that Akt2 is required for hepatic lipid accumulation in obese, insulin-resistant states induced by either leptin deficiency or high-fat diet feeding. Lep(ob/ob) mice lacking hepatic Akt2 failed to amass triglycerides in their livers, associated with and most likely due to a decrease in lipogenic gene expression and de novo lipogenesis. However, Akt2 is also required for steatotic pathways unrelated to fatty acid synthesis, as mice fed high-fat diet had reduced liver triglycerides in the absence of hepatic Akt2 but did not exhibit changes in lipogenesis. These data demonstrate that Akt2 is a requisite component of the insulin-dependent regulation of lipid metabolism during insulin resistance.
authors.affiliation: Department of Medicine, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Karla F
authors.initials: KF
authors.lastname: Leavens
authors.forename: Rachael M
authors.initials: RM
authors.lastname: Easton
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Previs
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Birnbaum
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D020738:Leptin; D014280:Triglycerides; C494922:Akt2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt