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High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature
Metabolic changes induced by high fat diet (HFD) that contribute to osteoarthritis (OA) are poorly understood. We investigated longitudinal changes to metabolites and their contribution to OA pathogenesis in response to HFD. HFD-fed mice exhibited acceleration of spontaneous age-related and surgical...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557929/ https://www.ncbi.nlm.nih.gov/pubmed/28811491 http://dx.doi.org/10.1038/s41598-017-07963-6 |
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author | Datta, Poulami Zhang, Yue Parousis, Alexa Sharma, Anirudh Rossomacha, Evgeny Endisha, Helal Wu, Brian Kacprzak, Izabela Mahomed, Nizar N. Gandhi, Rajiv Rockel, Jason S. Kapoor, Mohit |
author_facet | Datta, Poulami Zhang, Yue Parousis, Alexa Sharma, Anirudh Rossomacha, Evgeny Endisha, Helal Wu, Brian Kacprzak, Izabela Mahomed, Nizar N. Gandhi, Rajiv Rockel, Jason S. Kapoor, Mohit |
author_sort | Datta, Poulami |
collection | PubMed |
description | Metabolic changes induced by high fat diet (HFD) that contribute to osteoarthritis (OA) are poorly understood. We investigated longitudinal changes to metabolites and their contribution to OA pathogenesis in response to HFD. HFD-fed mice exhibited acceleration of spontaneous age-related and surgically-induced OA compared to lean diet (LD)-fed mice. Using metabolomics, we identified that HFD-fed mice exhibited a distinct and sustained plasma metabolite signature rich in phosphatidylcholines (PC) and lysophosphatidylcholines (lysoPCs), even after resumption of normal chow diet. Using receiver operator curve analysis and prediction modelling, we showed that the concentration of these identified metabolites could efficiently predict the type of diet and OA risk with an accuracy of 93%. Further, longitudinal evaluation of knee joints of HFD- compared to LD- fed mice showed a greater percentage of leptin-positive chondrocytes. Mechanistic data showed that leptin-treated human OA chondrocytes exhibited enhanced production of lysoPCs and expression of autotaxin and catabolic MMP-13. Leptin-induced increased MMP13 expression was reversed by autotaxin inhibition. Together, this study is the first to describe a distinct and sustained HFD-induced metabolite signature. This study suggests that in addition to increased weight, identified metabolites and local leptin-signaling may also contribute in part, towards the accelerated OA-phenotype observed in HFD mice. |
format | Online Article Text |
id | pubmed-5557929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55579292017-08-16 High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature Datta, Poulami Zhang, Yue Parousis, Alexa Sharma, Anirudh Rossomacha, Evgeny Endisha, Helal Wu, Brian Kacprzak, Izabela Mahomed, Nizar N. Gandhi, Rajiv Rockel, Jason S. Kapoor, Mohit Sci Rep Article Metabolic changes induced by high fat diet (HFD) that contribute to osteoarthritis (OA) are poorly understood. We investigated longitudinal changes to metabolites and their contribution to OA pathogenesis in response to HFD. HFD-fed mice exhibited acceleration of spontaneous age-related and surgically-induced OA compared to lean diet (LD)-fed mice. Using metabolomics, we identified that HFD-fed mice exhibited a distinct and sustained plasma metabolite signature rich in phosphatidylcholines (PC) and lysophosphatidylcholines (lysoPCs), even after resumption of normal chow diet. Using receiver operator curve analysis and prediction modelling, we showed that the concentration of these identified metabolites could efficiently predict the type of diet and OA risk with an accuracy of 93%. Further, longitudinal evaluation of knee joints of HFD- compared to LD- fed mice showed a greater percentage of leptin-positive chondrocytes. Mechanistic data showed that leptin-treated human OA chondrocytes exhibited enhanced production of lysoPCs and expression of autotaxin and catabolic MMP-13. Leptin-induced increased MMP13 expression was reversed by autotaxin inhibition. Together, this study is the first to describe a distinct and sustained HFD-induced metabolite signature. This study suggests that in addition to increased weight, identified metabolites and local leptin-signaling may also contribute in part, towards the accelerated OA-phenotype observed in HFD mice. Nature Publishing Group UK 2017-08-15 /pmc/articles/PMC5557929/ /pubmed/28811491 http://dx.doi.org/10.1038/s41598-017-07963-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Datta, Poulami Zhang, Yue Parousis, Alexa Sharma, Anirudh Rossomacha, Evgeny Endisha, Helal Wu, Brian Kacprzak, Izabela Mahomed, Nizar N. Gandhi, Rajiv Rockel, Jason S. Kapoor, Mohit High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature |
title | High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature |
title_full | High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature |
title_fullStr | High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature |
title_full_unstemmed | High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature |
title_short | High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature |
title_sort | high-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557929/ https://www.ncbi.nlm.nih.gov/pubmed/28811491 http://dx.doi.org/10.1038/s41598-017-07963-6 |
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