The potential adverse role of leptin resistance in nonalcoholic fatty liver disease: a hypothesis based on critical review of the literature.
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.
Polyzos
Stergios A
SA
Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece. stergios@endo.gr
Kountouras
Jannis
J
Zavos
Christos
C
Deretzi
Georgia
G
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
D020738:Leptin; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2