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Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NAS...

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Autores principales: Yoo, Wonbeak, Gjuka, Donjeta, Stevenson, Heather L., Song, Xiaoling, Shen, Hong, Yoo, Suk Young, Wang, Jing, Fallon, Michael, Ioannou, George N., Harrison, Stephen A., Beretta, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731750/
https://www.ncbi.nlm.nih.gov/pubmed/29244873
http://dx.doi.org/10.1371/journal.pone.0189965
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author Yoo, Wonbeak
Gjuka, Donjeta
Stevenson, Heather L.
Song, Xiaoling
Shen, Hong
Yoo, Suk Young
Wang, Jing
Fallon, Michael
Ioannou, George N.
Harrison, Stephen A.
Beretta, Laura
author_facet Yoo, Wonbeak
Gjuka, Donjeta
Stevenson, Heather L.
Song, Xiaoling
Shen, Hong
Yoo, Suk Young
Wang, Jing
Fallon, Michael
Ioannou, George N.
Harrison, Stephen A.
Beretta, Laura
author_sort Yoo, Wonbeak
collection PubMed
description Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD) NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD. Serum levels of 15:0, 17:0 and 16:1n7t negatively correlated with NAFLD activity scores and hepatocyte ballooning scores, while 18:1n7c serum levels strongly correlated with fibrosis stage and liver inflammation. Serum levels of 15:0 and 17:0 also negatively correlated with fasting glucose and AST, while 16:1n7c and 18:1n7c levels positively correlated with AST and ferritin, respectively. Inclusion of demographic and clinical parameters improved the performance of the fatty acid panels in detecting NASH in NAFLD patients. The panel [15:0, 16:1n7t, 18:1n7c, 22:5n3, age, ferritin and APRI] predicted intermediate or advanced fibrosis in NAFLD patients, with 82% sensitivity at 90% specificity [AUROC = 0.92]. 15:0 and 18:1n7c were further selected for functional studies in vivo. Mice treated with 15:0-supplemented MCD diet showed reduced AST levels and hepatic infiltration of ceroid-laden macrophages compared to MCD-treated mice, suggesting that 15:0 deficiency contributes to liver injury in NASH. In contrast, 18:1n7c-supplemented MCD diet didn’t affect liver pathology. In conclusion, 15:0 may serve as a promising biomarker or therapeutic target in NASH, opening avenues for the integration of diagnosis and treatment.
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spelling pubmed-57317502017-12-22 Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid Yoo, Wonbeak Gjuka, Donjeta Stevenson, Heather L. Song, Xiaoling Shen, Hong Yoo, Suk Young Wang, Jing Fallon, Michael Ioannou, George N. Harrison, Stephen A. Beretta, Laura PLoS One Research Article Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD) NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD. Serum levels of 15:0, 17:0 and 16:1n7t negatively correlated with NAFLD activity scores and hepatocyte ballooning scores, while 18:1n7c serum levels strongly correlated with fibrosis stage and liver inflammation. Serum levels of 15:0 and 17:0 also negatively correlated with fasting glucose and AST, while 16:1n7c and 18:1n7c levels positively correlated with AST and ferritin, respectively. Inclusion of demographic and clinical parameters improved the performance of the fatty acid panels in detecting NASH in NAFLD patients. The panel [15:0, 16:1n7t, 18:1n7c, 22:5n3, age, ferritin and APRI] predicted intermediate or advanced fibrosis in NAFLD patients, with 82% sensitivity at 90% specificity [AUROC = 0.92]. 15:0 and 18:1n7c were further selected for functional studies in vivo. Mice treated with 15:0-supplemented MCD diet showed reduced AST levels and hepatic infiltration of ceroid-laden macrophages compared to MCD-treated mice, suggesting that 15:0 deficiency contributes to liver injury in NASH. In contrast, 18:1n7c-supplemented MCD diet didn’t affect liver pathology. In conclusion, 15:0 may serve as a promising biomarker or therapeutic target in NASH, opening avenues for the integration of diagnosis and treatment. Public Library of Science 2017-12-15 /pmc/articles/PMC5731750/ /pubmed/29244873 http://dx.doi.org/10.1371/journal.pone.0189965 Text en © 2017 Yoo et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yoo, Wonbeak
Gjuka, Donjeta
Stevenson, Heather L.
Song, Xiaoling
Shen, Hong
Yoo, Suk Young
Wang, Jing
Fallon, Michael
Ioannou, George N.
Harrison, Stephen A.
Beretta, Laura
Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid
title Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid
title_full Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid
title_fullStr Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid
title_full_unstemmed Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid
title_short Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid
title_sort fatty acids in non-alcoholic steatohepatitis: focus on pentadecanoic acid
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731750/
https://www.ncbi.nlm.nih.gov/pubmed/29244873
http://dx.doi.org/10.1371/journal.pone.0189965
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