Steatosis does not impair liver regeneration after partial hepatectomy.
Hepatic steatosis is a key feature of non-alcoholic fatty liver disease (NAFLD). While storage of lipid droplet-bound triglycerides in simple steatosis is physiologically inert, non-alcoholic steatohepatitis (NASH) is associated with hepatocyte damage and apoptosis. Mitochondrial oxidation of free fatty acids (FFA), derived from lipid droplets and hepatocellular uptake, is a rapid and effective way of energy supply for proliferating cells and FFA esterification provides substrates for lipid synthesis and cell proliferation. Thus, we investigated whether simple steatosis induced by western diet (WD) improves liver regeneration after partial hepatectomy (PHx). WD feeding for 6 weeks caused simple steatosis with hepatic lipid droplet and triglyceride accumulation accompanied by induction of fatty acid transport proteins (FATP), death receptors (DR), pro- and anti-apoptotic genes, hepatocyte growth factor (Hgf) as well as increased serum leptin levels in a mouse model. After PHx, liver cell proliferation was higher in WD-fed mice and associated with FATP and Hgf induction. In addition, Erk1/2 (extracellular-related MAP kinase 1/2) dephosphorylation observed in standard diet (SD) mice was reduced in WD animals. PHx in steatotic livers did not affect hepatocyte apoptosis, despite DR upregulation. WD-induced steatosis enhances liver cell proliferation, which is accompanied by increased Hgf and leptin signaling as well as Erk1/2 phosphorylation. Induction of mild steatosis may therefore be beneficial for surgical outcome of hepatectomies.
Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
Svenja
S
Sydor
Yanli
Y
Gu
Martin
M
Schlattjan
Lars P
LP
Bechmann
Ursula
U
Rauen
Jan
J
Best
Andreas
A
Paul
Hideo A
HA
Baba
Jan-Peter
JP
Sowa
Guido
G
Gerken
Ali
A
Canbay
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat; D004951:Esterification; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000503:physiopathology*; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology*; D006651:Histocytochemistry; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D053218:Receptors, Death Domain / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D050612:Fatty Acid Transport Proteins; D053218:Receptors, Death Domain; D014280:Triglycerides