The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity

Abstract Dysfunctional visceral adipose tissue (VAT) in obesity is associated with type 2 diabetes (DM) but underlying mechanisms remain unclear. Our objective in this discovery analysis was to identify genes and proteins regulated by DM to elucidate aberrant cellular metabolic and signaling mediato...

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Autores principales:	Nicholas J. Carruthers, Clarissa Strieder-Barboza, Joseph A. Caruso, Carmen G. Flesher, Nicki A. Baker, Samuel A. Kerk, Alexander Ky, Anne P. Ehlers, Oliver A. Varban, Costas A. Lyssiotis, Carey N. Lumeng, Paul M. Stemmer, Robert W. O’Rourke
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/024c6a60909c4763a385cab961c87175
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spelling	oai:doaj.org-article:024c6a60909c4763a385cab961c871752021-12-02T15:28:52ZThe human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity10.1038/s41598-021-96995-02045-2322https://doaj.org/article/024c6a60909c4763a385cab961c871752021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96995-0https://doaj.org/toc/2045-2322Abstract Dysfunctional visceral adipose tissue (VAT) in obesity is associated with type 2 diabetes (DM) but underlying mechanisms remain unclear. Our objective in this discovery analysis was to identify genes and proteins regulated by DM to elucidate aberrant cellular metabolic and signaling mediators. We performed label-free proteomics and RNA-sequencing analysis of VAT from female bariatric surgery subjects with DM and without DM (NDM). We quantified 1965 protein groups, 23 proteins, and 372 genes that were differently abundant in DM vs. NDM VAT. Proteins downregulated in DM were related to fatty acid synthesis and mitochondrial function (fatty acid synthase, FASN; dihydrolipoyl dehydrogenase, mitochondrial, E3 component, DLD; succinate dehydrogenase-α, SDHA) while proteins upregulated in DM were associated with innate immunity and transcriptional regulation (vitronectin, VTN; endothelial protein C receptor, EPCR; signal transducer and activator of transcription 5B, STAT5B). Transcriptome indicated defects in innate inflammation, lipid metabolism, and extracellular matrix (ECM) function, and components of complement classical and alternative cascades. The VAT proteome and transcriptome shared 13 biological processes impacted by DM, related to complement activation, cell proliferation and migration, ECM organization, lipid metabolism, and gluconeogenesis. Our data revealed a marked effect of DM in downregulating FASN. We also demonstrate enrichment of complement factor B (CFB), coagulation factor XIII A chain (F13A1), thrombospondin 1 (THBS1), and integrins at mRNA and protein levels, albeit with lower q-values and lack of Western blot or PCR confirmation. Our findings suggest putative mechanisms of VAT dysfunction in DM.Nicholas J. CarruthersClarissa Strieder-BarbozaJoseph A. CarusoCarmen G. FlesherNicki A. BakerSamuel A. KerkAlexander KyAnne P. EhlersOliver A. VarbanCostas A. LyssiotisCarey N. LumengPaul M. StemmerRobert W. O’RourkeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicholas J. Carruthers Clarissa Strieder-Barboza Joseph A. Caruso Carmen G. Flesher Nicki A. Baker Samuel A. Kerk Alexander Ky Anne P. Ehlers Oliver A. Varban Costas A. Lyssiotis Carey N. Lumeng Paul M. Stemmer Robert W. O’Rourke The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity
description	Abstract Dysfunctional visceral adipose tissue (VAT) in obesity is associated with type 2 diabetes (DM) but underlying mechanisms remain unclear. Our objective in this discovery analysis was to identify genes and proteins regulated by DM to elucidate aberrant cellular metabolic and signaling mediators. We performed label-free proteomics and RNA-sequencing analysis of VAT from female bariatric surgery subjects with DM and without DM (NDM). We quantified 1965 protein groups, 23 proteins, and 372 genes that were differently abundant in DM vs. NDM VAT. Proteins downregulated in DM were related to fatty acid synthesis and mitochondrial function (fatty acid synthase, FASN; dihydrolipoyl dehydrogenase, mitochondrial, E3 component, DLD; succinate dehydrogenase-α, SDHA) while proteins upregulated in DM were associated with innate immunity and transcriptional regulation (vitronectin, VTN; endothelial protein C receptor, EPCR; signal transducer and activator of transcription 5B, STAT5B). Transcriptome indicated defects in innate inflammation, lipid metabolism, and extracellular matrix (ECM) function, and components of complement classical and alternative cascades. The VAT proteome and transcriptome shared 13 biological processes impacted by DM, related to complement activation, cell proliferation and migration, ECM organization, lipid metabolism, and gluconeogenesis. Our data revealed a marked effect of DM in downregulating FASN. We also demonstrate enrichment of complement factor B (CFB), coagulation factor XIII A chain (F13A1), thrombospondin 1 (THBS1), and integrins at mRNA and protein levels, albeit with lower q-values and lack of Western blot or PCR confirmation. Our findings suggest putative mechanisms of VAT dysfunction in DM.
format	article
author	Nicholas J. Carruthers Clarissa Strieder-Barboza Joseph A. Caruso Carmen G. Flesher Nicki A. Baker Samuel A. Kerk Alexander Ky Anne P. Ehlers Oliver A. Varban Costas A. Lyssiotis Carey N. Lumeng Paul M. Stemmer Robert W. O’Rourke
author_facet	Nicholas J. Carruthers Clarissa Strieder-Barboza Joseph A. Caruso Carmen G. Flesher Nicki A. Baker Samuel A. Kerk Alexander Ky Anne P. Ehlers Oliver A. Varban Costas A. Lyssiotis Carey N. Lumeng Paul M. Stemmer Robert W. O’Rourke
author_sort	Nicholas J. Carruthers
title	The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity
title_short	The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity
title_full	The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity
title_fullStr	The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity
title_full_unstemmed	The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity
title_sort	human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/024c6a60909c4763a385cab961c87175
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The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity

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