Propranolol impairs liver regeneration after partial hepatectomy in C57Bl/6-mice by transient attenuation of hepatic lipid accumulation and increased apoptosis

Abstract

Objective. Acute hepatic fat accumulation appears to be crucial for liver regeneration after partial hepatectomy. Since fatty acids in the liver are provided by catecholamine-induced lipolysis in the adipose tissue, we investigated whether β-adrenergic blockade of lipolysis might affect liver regeneration. Material and methods. Mice were treated with propranolol prior to partial hepatectomy. Subsequently, liver regeneration was evaluated histologically, by determination of the relative liver weight and the mitotic index at different time points after surgery. Results. Liver mass restoration was delayed by propranolol, which was associated with a lower hepatic triglyceride content. Ki-67 labelling indicated that liver regeneration was attenuated by propranolol through inhibition of mitosis. Hepatocytes were arrested in the G1 phase of the cell cycle, as shown by the expression of G1-related proteins such as proliferating cell nuclear antigen, cyclin D1 and cyclin-dependent kinase-2, and underwent apoptosis as indicated by detection of poly(adenosine diphosphate-ribose) polymerase fragments. β-adrenergic blockade of the host animal did not provide transplanted hepatocytes with a growth advantage over host cells. Conclusion. Impairment of liver regeneration by propranolol is related to the inhibition of acute hepatic fat accumulation and to a predisposition of hepatocytes to apoptosis.

Key Words::

• Beta-adrenergic inhibition
• hepatic fat accumulation
• hepatocyte transplantation
• liver regeneration
• partial hepatectomy

Acknowledgements

This project is supported by the German Ministry of Education and Research (to B. C.; contract grant number: NBL3-NG4) and the Federal State of Saxony-Anhalt and the German Ministry of Education and Research through the Wilhelm-Roux-Program at the Medical Faculty of the Martin-Luther-University of Halle-Wittenberg (to J. W.; grant number: 3/26).

Declaration of interest: The authors have no conflict of interest to declare.