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Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease

This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography...

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Published in:Archives of biochemistry and biophysics 2017-06, Vol.623-624, p.64-75
Main Authors: Horas H Nababan, Saut, Nishiumi, Shin, Kawano, Yuki, Kobayashi, Takashi, Yoshida, Masaru, Azuma, Takeshi
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description This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p 
doi_str_mv 10.1016/j.abb.2017.04.009
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We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p &lt; 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend &lt;0.001). Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. •Plasma and hepatic levels of free adrenic acid were markedly increased in a mouse model of steatohepatitis.•Adrenic acid supplementation enhanced cytokine and chemokine gene expression in hepatocytes.•High ALT levels were associated with higher plasma adrenic acid levels in NAFLD patients.</description><identifier>ISSN: 0003-9861</identifier><identifier>EISSN: 1096-0384</identifier><identifier>DOI: 10.1016/j.abb.2017.04.009</identifier><identifier>PMID: 28456640</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adrenic acid ; Adult ; Alanine aminotransferase ; Animals ; Chemokine ; Cytokines - analysis ; Cytokines - immunology ; Disease Models, Animal ; Disease Progression ; Fatty Acids, Unsaturated - analysis ; Fatty Acids, Unsaturated - blood ; Fatty Acids, Unsaturated - immunology ; Female ; Gene Expression Regulation ; Hep G2 Cells ; Humans ; Inflammation - blood ; Inflammation - genetics ; Inflammation - immunology ; Inflammation - pathology ; Inflammation Mediators - analysis ; Inflammation Mediators - blood ; Inflammation Mediators - immunology ; Lipids - analysis ; Lipids - blood ; Lipids - immunology ; Liquid chromatography/mass-spectrometry ; Liver - immunology ; Liver - pathology ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Non-alcoholic fatty liver disease ; Non-alcoholic Fatty Liver Disease - blood ; Non-alcoholic Fatty Liver Disease - genetics ; Non-alcoholic Fatty Liver Disease - immunology ; Non-alcoholic Fatty Liver Disease - pathology ; Oxidative Stress</subject><ispartof>Archives of biochemistry and biophysics, 2017-06, Vol.623-624, p.64-75</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. 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subjects Adrenic acid
Adult
Alanine aminotransferase
Animals
Chemokine
Cytokines - analysis
Cytokines - immunology
Disease Models, Animal
Disease Progression
Fatty Acids, Unsaturated - analysis
Fatty Acids, Unsaturated - blood
Fatty Acids, Unsaturated - immunology
Female
Gene Expression Regulation
Hep G2 Cells
Humans
Inflammation - blood
Inflammation - genetics
Inflammation - immunology
Inflammation - pathology
Inflammation Mediators - analysis
Inflammation Mediators - blood
Inflammation Mediators - immunology
Lipids - analysis
Lipids - blood
Lipids - immunology
Liquid chromatography/mass-spectrometry
Liver - immunology
Liver - pathology
Male
Mice
Mice, Inbred C57BL
Middle Aged
Non-alcoholic fatty liver disease
Non-alcoholic Fatty Liver Disease - blood
Non-alcoholic Fatty Liver Disease - genetics
Non-alcoholic Fatty Liver Disease - immunology
Non-alcoholic Fatty Liver Disease - pathology
Oxidative Stress
title Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease
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