Saut Horas H Nababan1, Shin Nishiumi2, Yuki Kawano1, Takashi Kobayashi1, Masaru Yoshida3, Takeshi Azuma1. 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.
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.
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.
Authors: Cyrielle Caussy; Jen-Chieh Chuang; Andrew Billin; Tao Hu; Ya Wang; G Mani Subramanian; C Stephen Djedjos; Robert P Myers; Edward A Dennis; Rohit Loomba Journal: Therap Adv Gastroenterol Date: 2020-05-26 Impact factor: 4.409
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