Mechanism of the development of nonalcoholic steatohepatitis after pancreaticoduodenectomy
| Autor: | Takahiro Yamaura, Frank J. Gonzalez, Tadanobu Nagaya, Toshifumi Aoyama, Takefumi Kimura, Naoki Tanaka, Hiroyuki Kitabatake, Kenji Sano, Michiharu Komatsu, Naoyuki Fujimori, Eiji Tanaka, Takeji Umemura, Akira Horiuchi |
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| Rok vydání: | 2014 |
| Předmět: |
Nonalcoholic steatohepatitis
medicine.medical_treatment BMI body mass index FASN fatty acid synthase PPAR peroxisome proliferator-activated receptor AST aspartate aminotransferase Gastroenterology Nonalcoholic fatty liver disease TNF tumor necrosis factor α CPT1A carnitine palmitoyl-CoA transferase 1α NAS NAFLD activity score TG triglyceride US ultrasonography MTTP microsomal triglyceride transfer protein SREBF1 sterol regulatory element-binding transcription factor 1 NASH Regular Article Hbv hepatitis b virus FABP fatty acid-binding protein γGT gamma-glutamyltransferase Pancreaticoduodenectomy CT computed tomography HADHA hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase α PPARGC PPARγ co-activator Alt alanine aminotransferase CYBB cytochrome b-245 β polypeptide HCV hepatitis C virus Molecular Medicine ACOX1 CYP cytochrome P450 LPS lipopolysaccharide MCD methionine- and choline-deficient diet qPCR quantitative polymerase chain reaction DGAT diacylglycerol acyltransferase NASH nonalcoholic steatohepatitis VLDL TLR Toll-like receptor CoA coenzyme A medicine.medical_specialty RXR retinoid X receptor NAFLD - Nonalcoholic Fatty Liver Disease digestive system Pathology and Forensic Medicine ROS reactive oxygen species SCD stearoyl-CoA desaturase PD pancreaticoduodenectomy Physiology (medical) Internal medicine ALT alanine aminotransferase SOD superoxide dismutase HOMA-IR homeostasis model assessment for insulin resistance medicine ApoB apolipoprotein B business.industry Mechanism (biology) FA fatty acid ACACB acetyl-CoA carboxylase β nutritional and metabolic diseases ACACA acetyl-CoA carboxylase α VLDL very-low-density lipoprotein ACADM medium-chain acyl-CoA dehydrogenase TGFB1 transforming growth factor β1 medicine.disease Fatty acid MyD88 digestive system diseases Endocrinology HBV hepatitis B virus ACOX1 acyl-CoA oxidase 1 NAFLD nonalcoholic fatty liver disease CAT catalase LXR liver X receptor business MYD88 myeloid differentiation primary response 88 |
| Zdroj: | BBA Clinical |
| ISSN: | 2214-6474 |
| Popis: | 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. Highlights • The mechanism of NASH development after pancreaticoduodenectomy (PD) was unclear. • The gene expression involved in fatty acid uptake and lipogenesis was increased. • PPARγ and its target genes were up-regulated in post-PD NASH livers. • Impaired triglyceride excretion from the liver was suggested in post-PD NASH. • This study proposes possible mechanisms of steatogenesis after PD. |
| Databáze: | OpenAIRE |
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