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Peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in NAFLD
BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is associated with mitochondrial dysfunction. This study aims to develop biomarkers for assessing mitochondrial dysfunction in patients with NAFLD. METHODS: Mitochondrion-associated transcriptome analysis was performed. Peripheral blood m...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637714/ https://www.ncbi.nlm.nih.gov/pubmed/36353244 http://dx.doi.org/10.3389/fendo.2022.967848 |
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author | Lee, A-Hyeon Oh, Ju Hee Kim, Hyun Sung Shin, Jeong-Hun Yoon, Eileen L. Jun, Dae Won |
author_facet | Lee, A-Hyeon Oh, Ju Hee Kim, Hyun Sung Shin, Jeong-Hun Yoon, Eileen L. Jun, Dae Won |
author_sort | Lee, A-Hyeon |
collection | PubMed |
description | BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is associated with mitochondrial dysfunction. This study aims to develop biomarkers for assessing mitochondrial dysfunction in patients with NAFLD. METHODS: Mitochondrion-associated transcriptome analysis was performed. Peripheral blood mononuclear cells obtained from patients with NAFLD (69) and healthy controls (19) were used to determine the mitochondrial DNA (mtDNA) copy number. A mitochondrial inhibition substrate test (ATP assay) was performed in HepG2 cells using the patient serum. RESULTS: Hepatic mRNA transcriptome analysis showed that the gene expression related to mitochondrial functions (mitochondrial fusion, apoptotic signal, and mitochondrial envelope) increased in patients with steatohepatitis, but not in those with NAFL. Gene set enrichment analysis revealed that the upregulated expression of genes is related to the pathways of the tricarboxylic (TCA) cycle and deoxyribonucleic acid (DNA) replication in patients with steatohepatitis, but not in healthy controls. The mtDNA copy number in the peripheral blood mononuclear cells was 1.28-fold lower in patients with NAFLD than that in healthy controls (P <.0001). The mitochondrial inhibition substrate test showed that the cellular adenosine triphosphate (ATP) concentration was 1.2-fold times less in NAFLD patients than that in healthy controls (P <.0001). The mtDNA copy number and mitochondrial ATP inhibition substrate test demonstrated negative correlations with the degree of hepatic steatosis, whereas the ATP concentration showed a positive correlation with the mtDNA copy number. CONCLUSION: The mitochondrial copy number of peripheral blood mononuclear cells and mitochondrial ATP inhibition substrate can be used as biomarkers for assessing the mitochondrial dysfunction in patients with NAFLD. |
format | Online Article Text |
id | pubmed-9637714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96377142022-11-08 Peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in NAFLD Lee, A-Hyeon Oh, Ju Hee Kim, Hyun Sung Shin, Jeong-Hun Yoon, Eileen L. Jun, Dae Won Front Endocrinol (Lausanne) Endocrinology BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is associated with mitochondrial dysfunction. This study aims to develop biomarkers for assessing mitochondrial dysfunction in patients with NAFLD. METHODS: Mitochondrion-associated transcriptome analysis was performed. Peripheral blood mononuclear cells obtained from patients with NAFLD (69) and healthy controls (19) were used to determine the mitochondrial DNA (mtDNA) copy number. A mitochondrial inhibition substrate test (ATP assay) was performed in HepG2 cells using the patient serum. RESULTS: Hepatic mRNA transcriptome analysis showed that the gene expression related to mitochondrial functions (mitochondrial fusion, apoptotic signal, and mitochondrial envelope) increased in patients with steatohepatitis, but not in those with NAFL. Gene set enrichment analysis revealed that the upregulated expression of genes is related to the pathways of the tricarboxylic (TCA) cycle and deoxyribonucleic acid (DNA) replication in patients with steatohepatitis, but not in healthy controls. The mtDNA copy number in the peripheral blood mononuclear cells was 1.28-fold lower in patients with NAFLD than that in healthy controls (P <.0001). The mitochondrial inhibition substrate test showed that the cellular adenosine triphosphate (ATP) concentration was 1.2-fold times less in NAFLD patients than that in healthy controls (P <.0001). The mtDNA copy number and mitochondrial ATP inhibition substrate test demonstrated negative correlations with the degree of hepatic steatosis, whereas the ATP concentration showed a positive correlation with the mtDNA copy number. CONCLUSION: The mitochondrial copy number of peripheral blood mononuclear cells and mitochondrial ATP inhibition substrate can be used as biomarkers for assessing the mitochondrial dysfunction in patients with NAFLD. Frontiers Media S.A. 2022-10-24 /pmc/articles/PMC9637714/ /pubmed/36353244 http://dx.doi.org/10.3389/fendo.2022.967848 Text en Copyright © 2022 Lee, Oh, Kim, Shin, Yoon and Jun https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Lee, A-Hyeon Oh, Ju Hee Kim, Hyun Sung Shin, Jeong-Hun Yoon, Eileen L. Jun, Dae Won Peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in NAFLD |
title | Peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in NAFLD |
title_full | Peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in NAFLD |
title_fullStr | Peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in NAFLD |
title_full_unstemmed | Peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in NAFLD |
title_short | Peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in NAFLD |
title_sort | peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in nafld |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637714/ https://www.ncbi.nlm.nih.gov/pubmed/36353244 http://dx.doi.org/10.3389/fendo.2022.967848 |
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