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.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Horas H Nababan S,Nishiumi S,Kawano Y,Kobayashi T,Yoshida M,Azuma Tdoi
10.1016/j.abb.2017.04.009subject
Has Abstractpub_date
2017-06-01 00:00:00pages
64-75eissn
0003-9861issn
1096-0384pii
S0003-9861(17)30147-9journal_volume
623-624pub_type
杂志文章abstract::The lysosomal cysteine proteinases, cathepsins B, H, and L, were all shown to bind to alpha 2-macroglobulin. The bound enzymes remained active against low-molecular-weight synthetic substrates and bound the active-site-directed inhibitor, benzyloxycarbonyl-125I-Tyr-Ala-diazomethane. Binding of the radiolabeled inhibit...
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journal_title:Archives of biochemistry and biophysics
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pub_type: 杂志文章
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