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

Cytokine. 2019 Dec;124:154569. doi: 10.1016/j.cyto.2018.10.010. Epub 2018 Oct 30.

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.

Keywords: Hepatic lipid metabolism; Liver; Liver cancer; NAFLD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Disease Models, Animal
  • Disease Progression
  • Growth Hormone / metabolism*
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism*
  • Lipid Metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Mice
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Receptors, Glucocorticoid / metabolism
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction / genetics

Substances

  • Receptors, Glucocorticoid
  • STAT5 Transcription Factor
  • Growth Hormone
  • Janus Kinase 2