Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies

Abstract Rosiglitazone is an effective insulin-sensitizer, however associated with bone loss mainly due to increased bone resorption and bone marrow adiposity. We investigated the effect of the co-administration of fish oil rich in omega-3 fatty acids (FAs) on rosiglitazone-induced bone loss in C57B...

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Autores principales:	Chiara Cugno, Dhanya Kizhakayil, Rita Calzone, Shaikh Mizanoor Rahman, Ganesh V. Halade, Md M. Rahman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13a37d9002684448ad36f36539e53ee4
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spelling	oai:doaj.org-article:13a37d9002684448ad36f36539e53ee42021-12-02T15:55:13ZOmega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies10.1038/s41598-021-89827-82045-2322https://doaj.org/article/13a37d9002684448ad36f36539e53ee42021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89827-8https://doaj.org/toc/2045-2322Abstract Rosiglitazone is an effective insulin-sensitizer, however associated with bone loss mainly due to increased bone resorption and bone marrow adiposity. We investigated the effect of the co-administration of fish oil rich in omega-3 fatty acids (FAs) on rosiglitazone-induced bone loss in C57BL/6 mice and the mechanisms underlying potential preventive effect. Mice fed the iso-caloric diet supplemented with fish oil exhibited significantly higher levels of bone density in different regions compared to the other groups. In the same cohort of mice, reduced activity of COX-2, enhanced activity of alkaline phosphatase, lower levels of cathepsin k, PPAR-γ, and pro-inflammatory cytokines, and a higher level of anti-inflammatory cytokines were observed. Moreover, fish oil restored rosiglitazone-induced down-regulation of osteoblast differentiation and up-regulation of adipocyte differentiation in C3H10T1/2 cells and inhibited the up-regulation of osteoclast differentiation of RANKL-treated RAW264.7 cells. We finally tested our hypothesis on human Mesenchymal Stromal Cells differentiated to osteocytes and adipocytes confirming the beneficial effect of docosahexaenoic acid (DHA) omega-3 FA during treatment with rosiglitazone, through the down-regulation of adipogenic genes, such as adipsin and FABP4 along the PPARγ/FABP4 axis, and reducing the capability of osteocytes to switch toward adipogenesis. Fish oil may prevent rosiglitazone-induced bone loss by inhibiting inflammation, osteoclastogenesis, and adipogenesis and by enhancing osteogenesis in the bone microenvironment.Chiara CugnoDhanya KizhakayilRita CalzoneShaikh Mizanoor RahmanGanesh V. HaladeMd M. RahmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chiara Cugno Dhanya Kizhakayil Rita Calzone Shaikh Mizanoor Rahman Ganesh V. Halade Md M. Rahman Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies
description	Abstract Rosiglitazone is an effective insulin-sensitizer, however associated with bone loss mainly due to increased bone resorption and bone marrow adiposity. We investigated the effect of the co-administration of fish oil rich in omega-3 fatty acids (FAs) on rosiglitazone-induced bone loss in C57BL/6 mice and the mechanisms underlying potential preventive effect. Mice fed the iso-caloric diet supplemented with fish oil exhibited significantly higher levels of bone density in different regions compared to the other groups. In the same cohort of mice, reduced activity of COX-2, enhanced activity of alkaline phosphatase, lower levels of cathepsin k, PPAR-γ, and pro-inflammatory cytokines, and a higher level of anti-inflammatory cytokines were observed. Moreover, fish oil restored rosiglitazone-induced down-regulation of osteoblast differentiation and up-regulation of adipocyte differentiation in C3H10T1/2 cells and inhibited the up-regulation of osteoclast differentiation of RANKL-treated RAW264.7 cells. We finally tested our hypothesis on human Mesenchymal Stromal Cells differentiated to osteocytes and adipocytes confirming the beneficial effect of docosahexaenoic acid (DHA) omega-3 FA during treatment with rosiglitazone, through the down-regulation of adipogenic genes, such as adipsin and FABP4 along the PPARγ/FABP4 axis, and reducing the capability of osteocytes to switch toward adipogenesis. Fish oil may prevent rosiglitazone-induced bone loss by inhibiting inflammation, osteoclastogenesis, and adipogenesis and by enhancing osteogenesis in the bone microenvironment.
format	article
author	Chiara Cugno Dhanya Kizhakayil Rita Calzone Shaikh Mizanoor Rahman Ganesh V. Halade Md M. Rahman
author_facet	Chiara Cugno Dhanya Kizhakayil Rita Calzone Shaikh Mizanoor Rahman Ganesh V. Halade Md M. Rahman
author_sort	Chiara Cugno
title	Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies
title_short	Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies
title_full	Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies
title_fullStr	Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies
title_full_unstemmed	Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies
title_sort	omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging c57bl/6 mice and in vitro studies
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/13a37d9002684448ad36f36539e53ee4
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Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies

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