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

Saut Horas H Nababan; Shin Nishiumi; Yuki Kawano; Takashi Kobayashi; Masaru Yoshida; Takeshi Azuma

doi:10.1016/j.abb.2017.04.009

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

Arch Biochem Biophys. 2017 Jun 1:623-624:64-75. doi: 10.1016/j.abb.2017.04.009. Epub 2017 Apr 26.

Authors

Saut Horas H Nababan¹, Shin Nishiumi², Yuki Kawano¹, Takashi Kobayashi¹, Masaru Yoshida³, Takeshi Azuma¹

Affiliations

¹ Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
² Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan. Electronic address: nishiums@med.kobe-u.ac.jp.
³ Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan; Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan; AMED-CREST, AMED, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.

PMID: 28456640
DOI: 10.1016/j.abb.2017.04.009

Abstract

Background: This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD).

Methods: 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.

Results: 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 < 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 <0.001).

Conclusion: Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD.

Keywords: Adrenic acid; Alanine aminotransferase; Chemokine; Liquid chromatography/mass-spectrometry; Non-alcoholic fatty liver disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
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
Liver / immunology
Liver / pathology*
Male
Mice
Mice, Inbred C57BL
Middle Aged
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

Substances

Cytokines
Fatty Acids, Unsaturated
Inflammation Mediators
Lipids
adrenic acid