摘要：Abstract Background and aim It is recognized that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), may develop after pancreaticoduodenectomy (PD). However, the mechanism of {NASH} development remains unclear. This study aimed to examine the changes in gene expression associated with {NASH} occurrence following PD. Methods The expression of genes related to fatty acid/triglyceride (FA/TG) metabolism and inflammatory signaling was examined using liver samples obtained from 7 post-PD {NASH} patients and compared with 6 healthy individuals and 32 conventional {NASH} patients. Results The livers of post-PD {NASH} patients demonstrated significant up-regulation of the genes encoding CD36, FA-binding proteins 1 and 4, acetyl-coenzyme A carboxylase α, diacylglycerol acyltransferase 2, and peroxisome proliferator-activated receptor (PPAR) γ compared with normal and conventional {NASH} livers. Although serum apolipoprotein B (ApoB) and {TG} were decreased in post-PD {NASH} patients, the mRNAs of ApoB and microsomal {TG} transfer protein were robustly increased, indicating impaired {TG} export from the liver as very-low-density lipoprotein (VLDL). Additionally, elevated mRNA levels of myeloid differentiation primary response 88 and superoxide dismutases in post-PD {NASH} livers suggested significant activation of innate immune response and augmentation of oxidative stress generation. Conclusions Enhanced {FA} uptake into hepatocytes and lipogenesis, up-regulation of PPARγ, and disruption of {VLDL} excretion into the circulation are possible mechanisms of steatogenesis after PD. General significance These results provide a basis for understanding the pathogenesis of NAFLD/NASH following PD.
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