Impaired liver regeneration in Ldlr-/- mice is associated with an altered hepatic profile of cytokines, growth factors, and lipids.

Abstract:

BACKGROUND & AIMS:It is widely recognized that in the early stages of liver regeneration after partial hepatectomy, the hepatocytes accumulate a significant amount of lipids. The functional meaning of this transient steatosis and its effect on hepatocellular proliferation are not well defined. In addition, the basic mechanisms of this lipid accumulation are not well understood although some studies suggest the participation of the Low Density Lipoprotein Receptor (Ldlr). METHODS:To address these questions, we studied the process of liver regeneration in Ldlr null mice and wild type mice following partial hepatectomy. RESULTS:Ldlr deficiency was associated with a significant decrease in serum albumin concentration, during early stages of liver regeneration, and a delayed hepatic regeneration. Remnant livers of Ldlr(-)(/)(-) showed a time-shifted expression of interleukin-6 (IL6) and a defective activation of tumor necrosis factor-α (TNFα) and hepatocyte growth factor (HGF) expression in early phases of liver regeneration. Unexpectedly, Ldlr(-)(/)(-) showed no significant differences in the content of lipid droplets after partial hepatectomy compared to wild type mice. However, lipidomic analysis of the regenerating liver from Ldlr(-)(/)(-) revealed a lipid profile compatible with liver quiescence: high content of cholesterol esters and ceramide, and low levels of phosphatidylcholine. CONCLUSIONS:Ldlr deficiency is associated with significant changes in the hepatic lipidome that affect cytokine-growth factor signaling and impair liver regeneration. These results suggest that the analysis of the hepatic lipidome may help predict the success of liver regeneration in the clinical environment, specifically in the context of pre-existing liver steatosis.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Pauta M,Rotllan N,Vales F,Fernandez-Hernando A,Allen RM,Ford DA,Marí M,Jiménez W,Baldán A,Morales-Ruiz M,Fernández-Hernando C

doi

10.1016/j.jhep.2013.05.026

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

731-7

issue

4

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(13)00358-9

journal_volume

59

pub_type

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