Schultze, Simon Manuel. The role of systemically perturbed PTEN and PKBß/AKT2 signaling in accumulation of hepatic lipids. 2013, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10498
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.
|Advisors:||Hall, Michael N.|
|Committee Members:||Hemmings, Brian A. and Wymann, Matthias Paul|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||119 S.|
|Last Modified:||30 Jun 2016 10:53|
|Deposited On:||02 Oct 2013 14:51|
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