GH administration rescues fatty liver regeneration impairment by restoring GH/EGFR pathway deficiency

Endocrinology. 2014 Jul;155(7):2545-54. doi: 10.1210/en.2014-1010. Epub 2014 Apr 7.


GH pathway has been shown to play a major role in liver regeneration through the control of epidermal growth factor receptor (EGFR) activation. This pathway is down-regulated in nonalcoholic fatty liver disease. Because regeneration is known to be impaired in fatty livers, we wondered whether a deregulation of the GH/EGFR pathway could explain this deficiency. Hepatic EGFR expression and triglyceride levels were quantified in liver biopsies of 32 obese patients with different degrees of steatosis. We showed a significant inverse correlation between liver EGFR expression and the level of hepatic steatosis. GH/EGFR down-regulation was also demonstrated in 2 steatosis mouse models, a genetic (ob/ob) and a methionine and choline-deficient diet mouse model, in correlation with liver regeneration defect. ob/ob mice exhibited a more severe liver regeneration defect after partial hepatectomy (PH) than methionine and choline-deficient diet-fed mice, a difference that could be explained by a decrease in signal transducer and activator of transcription 3 phosphorylation 32 hours after PH. Having checked that GH deficiency accounted for the GH signaling pathway down-regulation in the liver of ob/ob mice, we showed that GH administration in these mice led to a partial rescue in hepatocyte proliferation after PH associated with a concomitant restoration of liver EGFR expression and signal transducer and activator of trnascription 3 activation. In conclusion, we propose that the GH/EGFR pathway down-regulation is a general mechanism responsible for liver regeneration deficiency associated with steatosis, which could be partially rescued by GH administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Choline / metabolism
  • Diet
  • Down-Regulation / drug effects
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Fatty Liver / metabolism
  • Fatty Liver / physiopathology
  • Fatty Liver / prevention & control*
  • Hepatectomy / methods
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Human Growth Hormone / administration & dosage*
  • Human Growth Hormone / blood
  • Human Growth Hormone / deficiency
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Liver / surgery
  • Male
  • Methionine / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Non-alcoholic Fatty Liver Disease
  • Obesity / metabolism
  • Obesity / physiopathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Triglycerides / metabolism


  • STAT3 Transcription Factor
  • Triglycerides
  • Human Growth Hormone
  • Methionine
  • ErbB Receptors
  • Choline