Extracellular calcium modulates brown adipocyte differentiation and identity

Abstract Brown adipocytes are important in regulating non-shivering thermogenesis, whole body glucose and lipid homeostasis. Increasing evidence supports an important role of metabolites as well as macro- and micronutrients in brown adipocyte differentiation and function. Calcium is one of the most...

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Autores principales:	Ines Pramme-Steinwachs, Martin Jastroch, Siegfried Ussar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76263432c3334f9c8e0963cc343e4699
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spelling	oai:doaj.org-article:76263432c3334f9c8e0963cc343e46992021-12-02T15:06:23ZExtracellular calcium modulates brown adipocyte differentiation and identity10.1038/s41598-017-09025-32045-2322https://doaj.org/article/76263432c3334f9c8e0963cc343e46992017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09025-3https://doaj.org/toc/2045-2322Abstract Brown adipocytes are important in regulating non-shivering thermogenesis, whole body glucose and lipid homeostasis. Increasing evidence supports an important role of metabolites as well as macro- and micronutrients in brown adipocyte differentiation and function. Calcium is one of the most abundant ions in the body regulating multiple cellular processes. We observed that increasing extracellular calcium concentration during brown adipocyte differentiation blocks lipid accumulation and suppresses induction of major adipogenic transcription factors such as PPARγ and C/EBPα. In contrast, the depletion of calcium in the medium enhances adipogenesis and expression of brown adipocyte selective genes, such as UCP1. Mechanistically, we show that elevated extracellular calcium inhibits C/EBPβ activity through hyperactivation of ERK, a process that is independent of intracellular calcium levels and reversibly halts differentiation. Moreover, increased extracellular calcium solely after the induction phase of differentiation specifically suppresses gene expression of UCP1, PRDM16 and PGC1-α. Notably, depleting extracellular calcium provokes opposite effects. Together, we show that modulating extracellular calcium concentration controls brown adipocyte differentiation and thermogenic gene expression, highlighting the importance of tissue microenvironment on brown adipocyte heterogeneity and function.Ines Pramme-SteinwachsMartin JastrochSiegfried UssarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ines Pramme-Steinwachs Martin Jastroch Siegfried Ussar Extracellular calcium modulates brown adipocyte differentiation and identity
description	Abstract Brown adipocytes are important in regulating non-shivering thermogenesis, whole body glucose and lipid homeostasis. Increasing evidence supports an important role of metabolites as well as macro- and micronutrients in brown adipocyte differentiation and function. Calcium is one of the most abundant ions in the body regulating multiple cellular processes. We observed that increasing extracellular calcium concentration during brown adipocyte differentiation blocks lipid accumulation and suppresses induction of major adipogenic transcription factors such as PPARγ and C/EBPα. In contrast, the depletion of calcium in the medium enhances adipogenesis and expression of brown adipocyte selective genes, such as UCP1. Mechanistically, we show that elevated extracellular calcium inhibits C/EBPβ activity through hyperactivation of ERK, a process that is independent of intracellular calcium levels and reversibly halts differentiation. Moreover, increased extracellular calcium solely after the induction phase of differentiation specifically suppresses gene expression of UCP1, PRDM16 and PGC1-α. Notably, depleting extracellular calcium provokes opposite effects. Together, we show that modulating extracellular calcium concentration controls brown adipocyte differentiation and thermogenic gene expression, highlighting the importance of tissue microenvironment on brown adipocyte heterogeneity and function.
format	article
author	Ines Pramme-Steinwachs Martin Jastroch Siegfried Ussar
author_facet	Ines Pramme-Steinwachs Martin Jastroch Siegfried Ussar
author_sort	Ines Pramme-Steinwachs
title	Extracellular calcium modulates brown adipocyte differentiation and identity
title_short	Extracellular calcium modulates brown adipocyte differentiation and identity
title_full	Extracellular calcium modulates brown adipocyte differentiation and identity
title_fullStr	Extracellular calcium modulates brown adipocyte differentiation and identity
title_full_unstemmed	Extracellular calcium modulates brown adipocyte differentiation and identity
title_sort	extracellular calcium modulates brown adipocyte differentiation and identity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/76263432c3334f9c8e0963cc343e4699
work_keys_str_mv	AT inesprammesteinwachs extracellularcalciummodulatesbrownadipocytedifferentiationandidentity AT martinjastroch extracellularcalciummodulatesbrownadipocytedifferentiationandidentity AT siegfriedussar extracellularcalciummodulatesbrownadipocytedifferentiationandidentity
_version_	1718388455659012096

Extracellular calcium modulates brown adipocyte differentiation and identity

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