[PDF][PDF] Akt2 is required for hepatic lipid accumulation in models of insulin resistance
KF Leavens, RM Easton, GI Shulman, SF Previs… - Cell metabolism, 2009 - cell.com
Cell metabolism, 2009•cell.com
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 …
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 …
Summary
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. Lepob/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.
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