High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature

Abstract 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...

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Autores principales:	Poulami Datta, Yue Zhang, Alexa Parousis, Anirudh Sharma, Evgeny Rossomacha, Helal Endisha, Brian Wu, Izabela Kacprzak, Nizar N. Mahomed, Rajiv Gandhi, Jason S. Rockel, Mohit Kapoor
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/678dfc1b9a804ad2b4155ef14c5abcf2
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spelling	oai:doaj.org-article:678dfc1b9a804ad2b4155ef14c5abcf22021-12-02T11:41:22ZHigh-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature10.1038/s41598-017-07963-62045-2322https://doaj.org/article/678dfc1b9a804ad2b4155ef14c5abcf22017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07963-6https://doaj.org/toc/2045-2322Abstract 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.Poulami DattaYue ZhangAlexa ParousisAnirudh SharmaEvgeny RossomachaHelal EndishaBrian WuIzabela KacprzakNizar N. MahomedRajiv GandhiJason S. RockelMohit KapoorNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Poulami Datta Yue Zhang Alexa Parousis Anirudh Sharma Evgeny Rossomacha Helal Endisha Brian Wu Izabela Kacprzak Nizar N. Mahomed Rajiv Gandhi Jason S. Rockel Mohit Kapoor High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature
description	Abstract 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	article
author	Poulami Datta Yue Zhang Alexa Parousis Anirudh Sharma Evgeny Rossomacha Helal Endisha Brian Wu Izabela Kacprzak Nizar N. Mahomed Rajiv Gandhi Jason S. Rockel Mohit Kapoor
author_facet	Poulami Datta Yue Zhang Alexa Parousis Anirudh Sharma Evgeny Rossomacha Helal Endisha Brian Wu Izabela Kacprzak Nizar N. Mahomed Rajiv Gandhi Jason S. Rockel Mohit Kapoor
author_sort	Poulami Datta
title	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_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_sort	high-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/678dfc1b9a804ad2b4155ef14c5abcf2
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High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature

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