Akt2 is required for hepatic lipid accumulation in models of insulin resistance

Cell Metab. 2009 Nov;10(5):405-18. doi: 10.1016/j.cmet.2009.10.004.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Fats / administration & dosage
  • Insulin Resistance / physiology*
  • Leptin / antagonists & inhibitors
  • Leptin / genetics
  • Leptin / metabolism*
  • Lipid Metabolism / physiology*
  • Liver / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • Obesity / etiology
  • Obesity / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Triglycerides / metabolism

Substances

  • Dietary Fats
  • Leptin
  • Triglycerides
  • Akt2 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt