CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy

Abstract Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferas...

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Autores principales:	Xavier Roa-Mansergas, Rut Fadó, Maher Atari, Joan F. Mir, Helena Muley, Dolors Serra, Núria Casals
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9207a62a582b4db59d770e220fde6e21
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spelling	oai:doaj.org-article:9207a62a582b4db59d770e220fde6e212021-12-02T11:41:13ZCPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy10.1038/s41598-018-25485-72045-2322https://doaj.org/article/9207a62a582b4db59d770e220fde6e212018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25485-7https://doaj.org/toc/2045-2322Abstract Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferase 1 C (CPT1C) is a pseudoenzyme exclusively expressed in neurons and cancer cells. In the present study, we show that CPT1C is also expressed in hMSCs and protects them against glucose starvation, glycolysis inhibition, and oxygen/glucose deprivation. CPT1C overexpression in hMSCs did not increase fatty acid oxidation capacity, indicating that the role of CPT1C in these cells is different from that described in tumor cells. The increased survival of CPT1C-overexpressing hMSCs observed during glucose deficiency was found to be the result of autophagy enhancement, leading to a greater number of lipid droplets and increased intracellular ATP levels. In fact, inhibition of autophagy or lipolysis was observed to completely block the protective effects of CPT1C. Our results indicate that CPT1C-mediated autophagy enhancement in glucose deprivation conditions allows a greater availability of lipids to be used as fuel substrate for ATP generation, revealing a new role of CPT1C in stem cell adaptation to low nutrient environments.Xavier Roa-MansergasRut FadóMaher AtariJoan F. MirHelena MuleyDolors SerraNúria CasalsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xavier Roa-Mansergas Rut Fadó Maher Atari Joan F. Mir Helena Muley Dolors Serra Núria Casals CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy
description	Abstract Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferase 1 C (CPT1C) is a pseudoenzyme exclusively expressed in neurons and cancer cells. In the present study, we show that CPT1C is also expressed in hMSCs and protects them against glucose starvation, glycolysis inhibition, and oxygen/glucose deprivation. CPT1C overexpression in hMSCs did not increase fatty acid oxidation capacity, indicating that the role of CPT1C in these cells is different from that described in tumor cells. The increased survival of CPT1C-overexpressing hMSCs observed during glucose deficiency was found to be the result of autophagy enhancement, leading to a greater number of lipid droplets and increased intracellular ATP levels. In fact, inhibition of autophagy or lipolysis was observed to completely block the protective effects of CPT1C. Our results indicate that CPT1C-mediated autophagy enhancement in glucose deprivation conditions allows a greater availability of lipids to be used as fuel substrate for ATP generation, revealing a new role of CPT1C in stem cell adaptation to low nutrient environments.
format	article
author	Xavier Roa-Mansergas Rut Fadó Maher Atari Joan F. Mir Helena Muley Dolors Serra Núria Casals
author_facet	Xavier Roa-Mansergas Rut Fadó Maher Atari Joan F. Mir Helena Muley Dolors Serra Núria Casals
author_sort	Xavier Roa-Mansergas
title	CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy
title_short	CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy
title_full	CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy
title_fullStr	CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy
title_full_unstemmed	CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy
title_sort	cpt1c promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/9207a62a582b4db59d770e220fde6e21
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CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy

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