Disrupted hepatic adiponectin signaling impairs liver regeneration of steatotic rats.

Background: Individuals with non-alcohol fatty liver disease (NAFLD) exhibit impaired liver regeneration in a clinical setting and animal experiments. Adiponectin signaling is recognized as an important pathway of lipid metabolism, energy expenditure, 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), and a methionine-choline deficiency diet for 1 week (MCD 1W) and 5 weeks (MCD 5W), were used. The animals underwent 70% hepatectomy and were thereafter sacrificed at indicated time points.

Results: MCD 5W and HF displayed decreased Ki-67 labeling index and restituted liver mass compared to normal. Hepatic adiponectin, as well as TNF-α, of MCD5W and HF were increased compared to normal; whereas adiponectin receptor type 1 (AdipoR1) and adiponectin receptor type 2 (AdpoR2) were reciprocally decreased when compared to normal. PPARα, a downstream molecule of AdipoR2 axis, was decreased in MCD 5W compared to normal. Adenosine monophosphate- activated protein kinase (AMPK), a downstream molecule of AdipoR1 axis, was inactivated soon after hepatectomy in normal; whereas activation of AMPK persisted until day 3 after hepatectomy in MCD 5W and HF.

Conclusions: Reciprocal expression of adiponectin and its receptors in steatotic rats represents a unique form of adiponectin signaling disruption, which might be associated with impaired liver regeneration.