Propranolol impairs liver regeneration after partial hepatectomy in C57Bl/6-mice by transient attenuation of hepatic lipid accumulation and increased apoptosis.
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 beta-adrenergic blockade of lipolysis might affect liver regeneration.


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. beta-adrenergic blockade of the host animal did not provide transplanted hepatocytes with a growth advantage over host cells.


CONCLUSIONS
Impairment of liver regeneration by propranolol is related to the inhibition of acute hepatic fat accumulation and to a predisposition of hepatocytes to apoptosis.
Walldorf
Jens
J
First Department of Medicine, Martin-Luther University of Halle-Wittenberg, Halle/Saale, Germany.
Hillebrand
Christoph
C
Aurich
Hendryk
H
Stock
Peggy
P
Hempel
Madlen
M
Ebensing
Sabine
S
Fleig
Wolfgang E
WE
Seufferlein
Thomas
T
Dollinger
Matthias M
MM
Christ
Bruno
B
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle; D005234:Fatty Liver / Q000503:physiopathology*; D016193:G1 Phase; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation; D007150:Immunohistochemistry; D008115:Liver Regeneration / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011433:Propranolol / Q000494:pharmacology*
D011433:Propranolol