31
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

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

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

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Author and article information

          Comments

          Comment on this article