Steatosis is not sufficient to cause an impaired regenerative response after partial hepatectomy in rats.
OBJECTIVE
Fatty liver is known to be associated with increased mortality and morbidity after liver resection. The ability of fatty liver to regenerate after two-thirds partial hepatectomy was studied in three different models of steatosis in rats: obese Zucker rats, orotic acid-fed Wistar rats and Wistar rats fed a methionine-low, choline-deficient diet.


METHODS
Liver regeneration was assessed 24 h after partial hepatectomy by bromodeoxyuridine incorporation (immunohistochemistry), proliferating cell nuclear antigen, cyclin E and cyclin-dependent kinase 2 protein expression (Western blot analysis) and cyclin-dependent kinase 2 activity (kinase assays using histone H1 as a substrate).


RESULTS
No significant difference of proliferative response was found between orotic acid or methionine-low, choline-deficient diet-fed and control Wistar rats 24 h after partial hepatectomy. In contrast, hepatocyte proliferation in obese Zucker rats after partial hepatectomy was significantly reduced when compared with their lean controls.


CONCLUSIONS
Steatosis per se does not impair liver regeneration. The reduced liver regeneration observed in obese Zucker rats may not be due to fatty infiltration itself but to other factors such as leptin receptor dysfunction.
Picard
Christian
C
Gastroenterology Laboratory, Department of Gastroenterology, University of Louvain Medical School, Saint Luc University Hospital, Avenue Hippocrate 10, 1200 Brussels, Belgium.
Lambotte
Luc
L
Starkel
Peter
P
Sempoux
Christine
C
Saliez
Alain
A
Van den Berge
Véronique
V
Horsmans
Yves
Y
D000821:Animal Feed; D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D042846:CDC2-CDC28 Kinases; D002784:Cholesterol / Q000032:analysis; D002794:Choline; D019927:Cyclin E / Q000032:analysis; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D006498:Hepatectomy; D008099:Liver / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008715:Methionine; D009929:Organ Size; D009963:Orotic Acid; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D014280:Triglycerides / Q000032:analysis
D019927:Cyclin E; D018809:Proliferating Cell Nuclear Antigen; D014280:Triglycerides; D009963:Orotic Acid; D002784:Cholesterol; D008715:Methionine; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D001973:Bromodeoxyuridine; D002794:Choline