Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways

Abstract Brown adipose tissue function declines during aging and may contribute to the onset of metabolic disorders such as diabetes and obesity. Only limited understanding of the mechanisms leading to the metabolic impairment of brown adipocytes during aging exists. To this end, interscapular brown...

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Autores principales:	Carola Mancini, Sabrina Gohlke, Francisco Garcia-Carrizo, Vyacheslav Zagoriy, Heike Stephanowitz, Tim J. Schulz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cf9ff986f53a492da2a296b62f9b012a
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spelling	oai:doaj.org-article:cf9ff986f53a492da2a296b62f9b012a2021-12-02T18:37:11ZIdentification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways10.1038/s41598-021-99362-12045-2322https://doaj.org/article/cf9ff986f53a492da2a296b62f9b012a2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99362-1https://doaj.org/toc/2045-2322Abstract Brown adipose tissue function declines during aging and may contribute to the onset of metabolic disorders such as diabetes and obesity. Only limited understanding of the mechanisms leading to the metabolic impairment of brown adipocytes during aging exists. To this end, interscapular brown adipose tissue samples were collected from young and aged mice for quantification of differential gene expression and metabolite levels. To identify potential processes involved in brown adipocyte dysfunction, metabolite concentrations were correlated to aging and significantly changed candidates were subsequently integrated with a non-targeted proteomic dataset and gene expression analyses. Our results include novel age-dependent correlations of polar intermediates in brown adipose tissue. Identified metabolites clustered around three biochemical processes, specifically energy metabolism, nucleotide metabolism and vitamin metabolism. One mechanism of brown adipose tissue dysfunction may be linked to mast cell activity, and we identify increased histamine levels in aged brown fat as a potential biomarker. In addition, alterations of genes involved in synthesis and degradation of many metabolites were mainly observed in the mature brown adipocyte fraction as opposed to the stromal vascular fraction. These findings may provide novel insights on the molecular mechanisms contributing to the impaired thermogenesis of brown adipocytes during aging.Carola ManciniSabrina GohlkeFrancisco Garcia-CarrizoVyacheslav ZagoriyHeike StephanowitzTim J. SchulzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carola Mancini Sabrina Gohlke Francisco Garcia-Carrizo Vyacheslav Zagoriy Heike Stephanowitz Tim J. Schulz Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways
description	Abstract Brown adipose tissue function declines during aging and may contribute to the onset of metabolic disorders such as diabetes and obesity. Only limited understanding of the mechanisms leading to the metabolic impairment of brown adipocytes during aging exists. To this end, interscapular brown adipose tissue samples were collected from young and aged mice for quantification of differential gene expression and metabolite levels. To identify potential processes involved in brown adipocyte dysfunction, metabolite concentrations were correlated to aging and significantly changed candidates were subsequently integrated with a non-targeted proteomic dataset and gene expression analyses. Our results include novel age-dependent correlations of polar intermediates in brown adipose tissue. Identified metabolites clustered around three biochemical processes, specifically energy metabolism, nucleotide metabolism and vitamin metabolism. One mechanism of brown adipose tissue dysfunction may be linked to mast cell activity, and we identify increased histamine levels in aged brown fat as a potential biomarker. In addition, alterations of genes involved in synthesis and degradation of many metabolites were mainly observed in the mature brown adipocyte fraction as opposed to the stromal vascular fraction. These findings may provide novel insights on the molecular mechanisms contributing to the impaired thermogenesis of brown adipocytes during aging.
format	article
author	Carola Mancini Sabrina Gohlke Francisco Garcia-Carrizo Vyacheslav Zagoriy Heike Stephanowitz Tim J. Schulz
author_facet	Carola Mancini Sabrina Gohlke Francisco Garcia-Carrizo Vyacheslav Zagoriy Heike Stephanowitz Tim J. Schulz
author_sort	Carola Mancini
title	Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways
title_short	Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways
title_full	Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways
title_fullStr	Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways
title_full_unstemmed	Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways
title_sort	identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cf9ff986f53a492da2a296b62f9b012a
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Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways

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