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Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes

The biomechanics stress and chronic inflammation in obesity are causally linked to osteoarthritis. However, the metabolic factors mediating obesity-related osteoarthritis are still obscure. Here we scanned and identified at least two elevated metabolites (stearic acid and lactate) from the plasma of...

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Autores principales: Miao, Hongming, Chen, Liang, Hao, Lijun, Zhang, Xuan, Chen, Yujuan, Ruan, Zhihua, Liang, Houjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536527/
https://www.ncbi.nlm.nih.gov/pubmed/26271607
http://dx.doi.org/10.1038/srep13092
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author Miao, Hongming
Chen, Liang
Hao, Lijun
Zhang, Xuan
Chen, Yujuan
Ruan, Zhihua
Liang, Houjie
author_facet Miao, Hongming
Chen, Liang
Hao, Lijun
Zhang, Xuan
Chen, Yujuan
Ruan, Zhihua
Liang, Houjie
author_sort Miao, Hongming
collection PubMed
description The biomechanics stress and chronic inflammation in obesity are causally linked to osteoarthritis. However, the metabolic factors mediating obesity-related osteoarthritis are still obscure. Here we scanned and identified at least two elevated metabolites (stearic acid and lactate) from the plasma of diet-induced obese mice. We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1α protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes. Treatment with LDH-a and HIF1α inhibitors notably attenuated stearic acid-or high fat diet-stimulated proinflammatory cytokine production in vitro and in vivo. Furthermore, positive correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index was observed in subjects with osteoarthritis. In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1α pathway in chondrocytes. Our findings hold promise of developing novel clinical strategies for the management of obesity-related diseases such as osteoarthritis.
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spelling pubmed-45365272015-08-21 Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes Miao, Hongming Chen, Liang Hao, Lijun Zhang, Xuan Chen, Yujuan Ruan, Zhihua Liang, Houjie Sci Rep Article The biomechanics stress and chronic inflammation in obesity are causally linked to osteoarthritis. However, the metabolic factors mediating obesity-related osteoarthritis are still obscure. Here we scanned and identified at least two elevated metabolites (stearic acid and lactate) from the plasma of diet-induced obese mice. We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1α protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes. Treatment with LDH-a and HIF1α inhibitors notably attenuated stearic acid-or high fat diet-stimulated proinflammatory cytokine production in vitro and in vivo. Furthermore, positive correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index was observed in subjects with osteoarthritis. In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1α pathway in chondrocytes. Our findings hold promise of developing novel clinical strategies for the management of obesity-related diseases such as osteoarthritis. Nature Publishing Group 2015-08-14 /pmc/articles/PMC4536527/ /pubmed/26271607 http://dx.doi.org/10.1038/srep13092 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Miao, Hongming
Chen, Liang
Hao, Lijun
Zhang, Xuan
Chen, Yujuan
Ruan, Zhihua
Liang, Houjie
Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes
title Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes
title_full Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes
title_fullStr Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes
title_full_unstemmed Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes
title_short Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes
title_sort stearic acid induces proinflammatory cytokine production partly through activation of lactate-hif1α pathway in chondrocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536527/
https://www.ncbi.nlm.nih.gov/pubmed/26271607
http://dx.doi.org/10.1038/srep13092
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