Impaired liver regeneration of steatotic rats after portal vein ligation: a particular emphasis on (99m)Tc-DISIDA scintigraphy and adiponectin signaling

Abstract

Background & aims: Portal vein ligation (PVL) is increasingly employed prior to major hepatectomy in order to enhance the volume of the future liver remnant (FLR) and to avoid post-hepatectomy liver failure. The efficacy of PVL on subjects with non-alcohol fatty liver disease (NAFLD) is largely unknown.

Methods: Sprague-Dawley rats fed with normal diet (control) and methionine-choline deficient diet (MCD) were used. The animals underwent PVL and were sacrificed at indicated time points.

Results: Livers from MCD rats exhibited a decreased BrdU and Ki-67 labelling index, and an increased apoptotic index after PVL compared to normal rats; as a net effect, MCD rats exhibited a decrease in their restituted liver mass and redistributed volume ratio, compared to normal rats. Normal rats displayed similar serum levels of ICG15-R before and after PVL; whereas MCD rats displayed reduced ICG15-R after PVL. Using (99m)Tc-DISIDA scintigraphy examination, livers from MCD rats exhibited decreased HEF and prolonged TE(1/2) of FLR after PVL, indicating deteriorating hepatocyte function despite the shift in volume. The basal level of plasma TNFalpha, IL-1alpha, IL-1beta, and IL-10 of MCD rats was significantly increased before PVL compared to normal rats; however their plasma level did not increase in response to PVL as in normal rats. Hepatic adiponectin mRNA surged in MCD rats after PVL, whereas its receptors, AdipoR1 and AdipoR2, were paradoxically down-regulated. PPARalpha, a down-stream molecule of AdipoR2 axis, was also decreased in MCD rats.

Conclusions: Reduced regenerated liver mass and deteriorated hepatocyte function of the FLR from steatotic rats after PVL may be associated with deranged Kupffer cell-mediated cytokine expression and disrupted adiponectin signalling.