Disrupted Hepatic Adiponectin Signaling Impairs Liver Regeneration of Steatotic Rats

Background: Individuals with non-alcohol fatty liver disease (NAFLD) exhibit impairedliver regeneration in a clinical setting and animal experiments. Adiponectinsignaling is recognized as an important pathway of lipid metabolism, energyexpenditure, anti-inflammation, and cellular proliferation. We herein investigate hepatic adiponectin signaling in dietary steatotic murine models undergoing hepatectomy, which has never been explored.Methods: Sprague-Dawley rats fed with a normal diet (normal), high fat diet (HF), anda methionine-choline deficiency diet for 1 week (MCD 1W) and 5 weeks(MCD 5W), were used. The animals underwent 70% hepatectomy and werethereafter sacrificed at indicated time points.Results: MCD 5W and HF displayed decreased Ki-67 labeling index and restitutedliver mass compared to normal. Hepatic adiponectin, as well as TNF-α, ofMCD5W and HF were increased compared to normal; whereas adiponectinreceptor type 1 (AdipoR1) and adiponectin receptor type 2 (AdpoR2) werereciprocally decreased when compared to normal. PPARα, a downstreammolecule of AdipoR2 axis, was decreased in MCD 5W compared to normal.Adenosine monophosphate- activated protein kinase (AMPK), a downstreammolecule of AdipoR1 axis, was inactivated soon after hepatectomy in normal; whereas activation of AMPK persisted until day 3 after hepatectomy inMCD 5W and HF.Conclusions: Reciprocal expression of adiponectin and its receptors in steatotic rats represents a unique form of adiponectin signaling disruption, which might beassociated with impaired liver regeneration