Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity

Abstract Obesity and the metabolic disease epidemic has led to an increase in morbidity and mortality. A rise in adipose thermogenic capacity via activation of brown or beige fat is a potential treatment for metabolic diseases. However, an understanding of how local factors control adipocyte fate is...

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Autores principales:	Maria A. Gonzalez Porras, Katerina Stojkova, Marcella K. Vaicik, Amanda Pelowe, Anna Goddi, Alanis Carmona, Byron Long, Amina A. Qutub, Anjelica Gonzalez, Ronald N. Cohen, Eric M. Brey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3451950b09ec48718aecf16f21d6e0f5
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spelling	oai:doaj.org-article:3451950b09ec48718aecf16f21d6e0f52021-12-02T15:52:58ZIntegrins and extracellular matrix proteins modulate adipocyte thermogenic capacity10.1038/s41598-021-84828-z2045-2322https://doaj.org/article/3451950b09ec48718aecf16f21d6e0f52021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84828-zhttps://doaj.org/toc/2045-2322Abstract Obesity and the metabolic disease epidemic has led to an increase in morbidity and mortality. A rise in adipose thermogenic capacity via activation of brown or beige fat is a potential treatment for metabolic diseases. However, an understanding of how local factors control adipocyte fate is limited. Mice with a null mutation in the laminin α4 (LAMA4) gene (KO) exhibit resistance to obesity and enhanced expression of thermogenic fat markers in white adipose tissue (WAT). In this study, changes in WAT extracellular matrix composition in the absence of LAMA4 were evaluated using liquid chromatography/tandem mass spectrometry. KO-mice showed lower levels of collagen 1A1 and 3A1, and integrins α7 (ITA7) and β1 (ITB1). ITA7-ITB1 and collagen 1A1-3A1 protein levels were lower in brown adipose tissue compared to WAT in wild-type mice. Immunohistochemical staining confirmed lower levels and different spatial distribution of ITA7 in KO-WAT. In culture studies, ITA7 and LAMA4 levels decreased following a 12-day differentiation of adipose-derived stem cells into beige fat, and knock-down of ITA7 during differentiation increased beiging. These results demonstrate that extracellular matrix interactions regulate adipocyte thermogenic capacity and that ITA7 plays a role in beige adipose formation. A better understanding of the mechanisms underlying these interactions can be used to improve systemic energy metabolism and glucose homeostasis.Maria A. Gonzalez PorrasKaterina StojkovaMarcella K. VaicikAmanda PeloweAnna GoddiAlanis CarmonaByron LongAmina A. QutubAnjelica GonzalezRonald N. CohenEric M. BreyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria A. Gonzalez Porras Katerina Stojkova Marcella K. Vaicik Amanda Pelowe Anna Goddi Alanis Carmona Byron Long Amina A. Qutub Anjelica Gonzalez Ronald N. Cohen Eric M. Brey Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity
description	Abstract Obesity and the metabolic disease epidemic has led to an increase in morbidity and mortality. A rise in adipose thermogenic capacity via activation of brown or beige fat is a potential treatment for metabolic diseases. However, an understanding of how local factors control adipocyte fate is limited. Mice with a null mutation in the laminin α4 (LAMA4) gene (KO) exhibit resistance to obesity and enhanced expression of thermogenic fat markers in white adipose tissue (WAT). In this study, changes in WAT extracellular matrix composition in the absence of LAMA4 were evaluated using liquid chromatography/tandem mass spectrometry. KO-mice showed lower levels of collagen 1A1 and 3A1, and integrins α7 (ITA7) and β1 (ITB1). ITA7-ITB1 and collagen 1A1-3A1 protein levels were lower in brown adipose tissue compared to WAT in wild-type mice. Immunohistochemical staining confirmed lower levels and different spatial distribution of ITA7 in KO-WAT. In culture studies, ITA7 and LAMA4 levels decreased following a 12-day differentiation of adipose-derived stem cells into beige fat, and knock-down of ITA7 during differentiation increased beiging. These results demonstrate that extracellular matrix interactions regulate adipocyte thermogenic capacity and that ITA7 plays a role in beige adipose formation. A better understanding of the mechanisms underlying these interactions can be used to improve systemic energy metabolism and glucose homeostasis.
format	article
author	Maria A. Gonzalez Porras Katerina Stojkova Marcella K. Vaicik Amanda Pelowe Anna Goddi Alanis Carmona Byron Long Amina A. Qutub Anjelica Gonzalez Ronald N. Cohen Eric M. Brey
author_facet	Maria A. Gonzalez Porras Katerina Stojkova Marcella K. Vaicik Amanda Pelowe Anna Goddi Alanis Carmona Byron Long Amina A. Qutub Anjelica Gonzalez Ronald N. Cohen Eric M. Brey
author_sort	Maria A. Gonzalez Porras
title	Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity
title_short	Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity
title_full	Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity
title_fullStr	Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity
title_full_unstemmed	Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity
title_sort	integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3451950b09ec48718aecf16f21d6e0f5
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_version_	1718385563129610240

Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity

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