title: The potential adverse role of leptin resistance in nonalcoholic fatty liver disease: a hypothesis based on critical review of the literature.
abstract: BACKGROUND
  Leptin is an adipocyte-derived hormone that plays a crucial role in energy homeostasis and lipid metabolism. Most of the biological effects of leptin are exerted through activation of the Janus kinase-2/signal transducer and activator of transcription-3 pathway. Signal transducer and activator of transcription-3 activation ultimately leads to an increased transcription and expression of suppressors of cytokine signaling-3, which acts as a feedback inhibitor by attenuating leptin signaling. Apart from inhibiting leptin signaling, suppressor of cytokine signaling-3 inhibits insulin signaling. Leptin increases with increasing fatty mass as a compensatory mechanism to preserve insulin sensitivity, but persistent hyperleptinemia is implicated in liver fibrinogenesis and carcinogenesis.
  
  
  OBJECTIVE
  Considering this dual role of leptin in the liver pathophysiology, we hypothesized that leptin resistance may vary according to the different types of liver cells and nonalcoholic fatty liver disease progression.
  
  
  CONCLUSIONS
  It is speculated that recombinant leptin, proposed to be used in common forms of obesity or nonalcoholic fatty liver disease, might have serious unfavorable therapeutical drawbacks, through promotion of insulin resistance, fibrosis, and hepatocellular carcinoma.
authors: Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece. stergios@endo.gr
authors: Stergios A
authors: SA
authors: Polyzos
authors: Jannis
authors: J
authors: Kountouras
authors: Christos
authors: C
authors: Zavos
authors: Georgia
authors: G
authors: Deretzi
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D018450:Disease Progression; D005234:Fatty Liver / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000209:etiology; D008113:Liver Neoplasms / Q000209:etiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020738:Leptin; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2