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
Citations
More filters
Journal ArticleDOI
PI3K/Akt signaling in osteosarcoma.
TL;DR: The aim of this review is to summarize the roles of the PI3K/Akt pathway in the development and progression of OS, and to highlight the therapeutic potential of targeting this signaling pathway.
Journal ArticleDOI
Redox balance in the pathogenesis of nonalcoholic fatty liver disease: mechanisms and therapeutic opportunities.
TL;DR: Intacellular mechanisms, including mitochondrial dysfunction and impaired oxidative free fatty acid metabolism, leading to reactive oxygen species generation, and the potential pathogenetic role of extracellular sources of reactive oxygen Species in NAFLD, including increased myeloperoxidase activity and oxidized low density lipoprotein accumulation, will be reviewed.
Journal ArticleDOI
Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach.
Fatih Mehmet Kandemir,Serkan Yildirim,Sefa Kucukler,Cuneyt Caglayan,Ekrem Darendelioglu,Muhammet Bahaeddin Dortbudak +5 more
TL;DR: Morin treatment attenuated the ACR-induced hepatorenal tissue injury by diminishing the serum AST, ALP, ALT, urea and creatinine levels and affected the protein levels by regulating the PI3K/Akt/mTOR signaling pathway and thus alleviated ACr-induced apoptosis and autophagy.
Journal Article
Signal transductions and nonalcoholic fatty liver: a mini-review.
TL;DR: In-depth study of the signal transductions will probably provide new suitable solutions for the prevention and therapy of NAFLD.
Journal ArticleDOI
Beneficial effects of paeoniflorin on non-alcoholic fatty liver disease induced by high-fat diet in rats
TL;DR: It is found that paeoniflorin has therapeutic potential against NAFLD and that it acts through multiple signaling pathways, including regulating lipid metabolism and exerting insulin sensitizing effect by regulating the insulin signaling pathway IRS/Akt/GSK3β and anti-oxidation.
References
More filters
Journal ArticleDOI
Non-alcoholic fatty liver disease
Briohny W. Smith,Leon A. Adams +1 more
TL;DR: Treatment of NAFLD revolves around addressing concomitant metabolic risk factors and improving insulin resistance through weight loss measures and exercise and shows some promise in improving liver histology in patients with NASH, however, the long-term benefit of these medications has not been demonstrated.
Journal ArticleDOI
High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo.
Sudheer K. Mantena,Denty Paul Vaughn,Kelly K. Andringa,Heather B. Eccleston,Adrienne L. King,Gary A. Abrams,Jeannette E. Doeller,David W. Kraus,Victor M. Darley-Usmar,Shannon M. Bailey +9 more
TL;DR: It is hypothesized that mitochondrial defects induced by exposure to a HFD (high fat diet) contribute to a hypoxic state in liver and this is associated with increased protein modification by RNS (reactive nitrogen species).
Journal ArticleDOI
Mitochondrial ROS generation for regulation of autophagic pathways in cancer.
TL;DR: A better understanding of the intricate relationships between mitochondrial ROS and autophagy may ultimately allow cancer biologists to harness mitochondrial ROS-mediated autophagic pathways for cancer drug discovery.
Journal ArticleDOI
A Versatile Role of Mammalian Target of Rapamycin in Human Dendritic Cell Function and Differentiation
Michael Haidinger,Marko Poglitsch,René Geyeregger,Sudhir Pai Kasturi,Maximilian Zeyda,Gerhard J. Zlabinger,Bali Pulendran,Walter H. Hörl,Marcus D. Säemann,Thomas Weichhart +9 more
TL;DR: Divergent roles of mTOR during activation and differentiation of myeloid DCs and monocyte-derived DCs are demonstrated and it is found that kidney transplant patients treated with rapamycin displayed an increased immunostimulatory potential of mDCs compared with patients treating with calcineurin inhibitors.
Journal ArticleDOI
PTEN and GSK3β : Key regulators of progression to androgen-independent prostate cancer
TL;DR: It is emphasized that temporal changes in GSK3β and PTEN expression during progression to AI PrCa are important factors when considering the potential for therapies targeting the oncogenic contributions of PI3K/Akt and AR signalling pathways.