Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease
TLDR
Molecular studies in the NAFLD support a key role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis, and fibrosis, and review recent studies on the features of the PTEN and the PI3K/AKT pathway.Abstract:
Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver pathologies and is associated with obesity and the metabolic syndrome, which represents a range of fatty liver diseases associated with an increased risk of type 2 diabetes. Molecular mechanisms underlying how to make transition from simple fatty liver to nonalcoholic steatohepatitis (NASH) are not well understood. However, accumulating evidence indicates that deregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in hepatocytes is a common molecular event associated with metabolic dysfunctions including obesity, metabolic syndrome, and the NAFLD. A tumor suppressor PTEN negatively regulates the PI3K/AKT pathways through its lipid phosphatase activity. Molecular studies in the NAFLD support a key role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis, and fibrosis. We review recent studies on the features of the PTEN and the PI3K/AKT pathway and discuss the protein functions in the signaling pathways involved in the NAFLD. The molecular mechanisms contributing to the diseases are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to novel therapies for a condition.read more
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References
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Journal ArticleDOI
Identification of novel PTEN-binding partners: PTEN interaction with fatty acid binding protein FABP4
Olena Gorbenko,George Panayotou,Alexander Zhyvoloup,Darija Volkova,Ivan Gout,Valeriy Filonenko +5 more
TL;DR: The demonstrable tautology of PTEN to FABP4 suggested a role for this phosphatase in the regulation of lipid metabolism and adipocyte differentiation, and the KD ofPTEN–FABP 4 complex is calculated, which is around 2.8 μM.
Journal ArticleDOI
Shiga Toxin 1-Induced Proinflammatory Cytokine Production Is Regulated by the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway
TL;DR: The findings suggest that despite transient activation of 4E-BP, the PI3K/Akt/mTOR pathway negatively influences cytokine induction by inactivating the positive regulator GSK-3α/β.
Journal ArticleDOI
Hypoxia and non-alcoholic fatty liver disease
TL;DR: It is shown that a short period (7 days) of exposure to hypoxia aggravates the NAFLD phenotype, causing changes in the liver that are in keeping with NASH with increased lipogenesis and inflammation.
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Progesterone Receptor-B Induction of BIRC3 Protects Endometrial Cancer Cells from AP1-59-Mediated Apoptosis
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TL;DR: The findings indicate a mechanism by which PRB can promote cell survival in the setting of high AKT activity in endometrial cancer cells, and an antagonist to IAPs, a second mitochondria-derived activator of caspase mimetic.
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Glycogen synthase kinase-3 beta inhibitor suppresses Porphyromonas gingivalis lipopolysaccharide-induced CD40 expression by inhibiting nuclear factor-kappa B activation in mouse osteoblasts.
TL;DR: The results elucidate the molecular mechanisms whereby GSK-3β inhibitor prevents the LPS-induced CD40 expression on osteoblasts and provide supportive evidence of the potential role of GSK -3β inhibitors in suppressing the immune function of osteoblast in inflammatory bone diseases.