Hepatic growth hormone - JAK2 - STAT5 signalling: Metabolic function, non-alcoholic fatty liver disease and hepatocellular carcinoma progression. (December 2019)

• Record Type: Journal Article
• Authors: Kaltenecker, Doris; Themanns, Madeleine; Mueller, Kristina M.; Spirk, Katrin; Suske, Tobias; Merkel, Olaf; Kenner, Lukas; Luís, Andreia; Kozlov, Andrey; Haybaeck, Johannes; Müller, Mathias; Han, Xiaonan; Moriggl, Richard
• Is Part Of: Cytokine. Volume 124(2019)
• Publication Date: 2019-12
• Subjects: Liver -- Hepatic lipid metabolism -- NAFLD -- Liver cancer; ACC Acetyl-CoA carboxylase -- Akt v-Akt murine thymoma viral oncogene homolog -- ALS Acid labile subunit -- ATP Adenosin triphosphate -- CCL4 Tetrachloride -- CDK Cyclin-dependent kinase -- cJun Cellular Jun -- DEN Diethylnitrosamine -- EGF Epidermal growth factor -- ERK Extracellular signal-regulated kinase -- FA Fatty Acid -- FAS/Fasn Fatty acid synthase -- Fatp1 Fatty acid transport protein 1 -- FGF Fibroblast growth factor -- GC Glucocorticoids -- GH Growth Hormone -- GHR Growth hormone receptor -- GR Glucocorticoid receptor -- GST Glutathione S-transferase -- HBV Hepatitis B virus -- HCV Hepatitis C virus -- HGF Hepatocyte growth factor -- HCC Hepatocellular carcinoma -- IGF Insulin-like growth factor -- JAK Janus kinase -- JNK c-Jun N-terminal kinase -- MAPK Mitogen-activated protein kinase -- mTOR Mammalian target of rapamycin -- NAFL Non-alcoholic fatty liver -- NAFLD Non-alcoholic fatty liver disease -- NASH Non-alcoholic steatohepatitis -- NOX NADPH-Oxidase -- PI3K Phosphoinositide 3-kinase -- PDGF Platelet-derived growth factor -- PPARγ Peroxisome proliferator-activated receptor gamma -- SCD Stearoyl-CoA desaturase -- RAS Rat sarcoma -- RB Retinoblastoma protein -- SOCS Cytokine signalling -- ROS Reactive oxygen species -- SH2 Src homology 2 -- SREBP sterol regulatory element-binding protein -- STAT Signal transducer and activator of transcription -- T2D Type 2 diabetes -- TGF-β Transforming growth factor beta -- VEGF Vascular endothelial growth factor -- WAT White adipose tissue -- WNT Wingless/Integrated; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2018.10.010
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Disruption of GH-JAK2-STAT5 signalling induces hepatic steatosis. Hepatic STAT5 executes tumour suppressive functions in HCC development. Hepatic JAK2 exerts oncogenic functions in HCC development. Divergent role of GH signalling in oxidative stress and damage management. Abstract: The rising prevalence of obesity came along with an increase in associated metabolic disorders in Western countries. Non-alcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of the metabolic syndrome and is linked to primary stages of liver cancer development. Growth hormone (GH) regulates various vital processes such as energy supply and cellular regeneration. In addition, GH regulates various aspects of liver physiology through activating the Janus kinase (JAK) 2- signal transducer and activator of transcription (STAT) 5 pathway. Consequently, disrupted GH - JAK2 - STAT5 signaling in the liver alters hepatic lipid metabolism and is associated with NAFLD development in humans and mouse models. Interestingly, while STAT5 as well as JAK2 deficiency correlates with hepatic lipid accumulation, recent studies suggest that these proteins have unique ambivalent functions in chronic liver disease progression and tumorigenesis. In this review, we focus on the consequences of altered GH - JAK2 - STAT5 signaling for hepatic lipid metabolism and liver cancer development with an emphasis on lessons learned from genetic knockout models.