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- W1567291778 abstract "Non-alcoholic fatty liver disease (NAFLD) is a major health problem and occurs frequently in the context of obesity and type 2 diabetes mellitus (T2D). Insulin resistance of the liver and/or peripheral tissues is considered to drive ectopic lipid accumulation in hepatocytes, but individual contributions are not fully understood. Hepatocyte-specific Pten-deficiency in mice was shown previously to result in hepatic steatosis due to hyperactivated PKBb in the liver. However, the role of peripheral insulin sensitive tissues on PTEN/PKBb-dependent development of NAFLD has not been addressed. The aim of this thesis is to characterize the effects of systemically perturbed PTEN/PKBb signaling on hepatic lipid content using Pten-haplodeficient (Pten+/-/Pkbb+/+) mice and Pten-haplodeficient mice lacking Pkbb (Pten+/-/Pkbb-/-). We found that Pten+/-/Pkbb+/+ mice have a more than 2-fold reduction in hepatic lipid content compared to control mice, similar to the low level observed in Pten+/-/Pkbb-/- mice. Pten+/-/Pkbb+/+ mice showed enhanced insulin signaling in the liver indicating that extra-hepatic factors prevent hepatic lipid accumulation. Further results suggested that augmented PKBb activity in the skeletal muscle of Pten+/-/Pkbb+/+ mice might reduce hepatic lipid content. Indeed, skeletal muscle-specific expression of constitutively active PKBb reduced hepatic lipids in Pten+/+Pkbb+/+ mice and dominant negative PKBb increased hepatic lipid content in both Pten+/+Pkbb+/+ and Pten+/-/Pkbb+/+ mice. The results obtained during this study show that PKBb activity in skeletal muscle regulates lipid accumulation in the livers of Pten+/+Pkbb+/+ and Pten+/-/Pkbb+/+ mice, and emphasizes the role of skeletal muscle in the pathophysiology of NAFLD." @default.
- W1567291778 created "2016-06-24" @default.
- W1567291778 creator A5015332423 @default.
- W1567291778 date "2013-01-01" @default.
- W1567291778 modified "2023-09-24" @default.
- W1567291778 title "The role of systemically perturbed PTEN and PKBß/AKT2 signaling in accumulation of hepatic lipids" @default.
- W1567291778 doi "https://doi.org/10.5451/unibas-006163864" @default.
- W1567291778 hasPublicationYear "2013" @default.
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