38ccfed0a2981a409f3831a9e9a40bf8 303862.pdf 21b78b6c63a92d979aff09cf273ec47965b8ba55 303862.pdf bc359b585e91f81e2235c7cc7e4b6694249c5be2209ea8284092efbea6c8b37f 303862.pdf Title: Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles Subject: Obesity is associated with metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM), further increasing an already heightened cardiovascular risk. Here, amongst obese class III bariatric surgery patients, we have investigated the effect of T2DM in serum and in two, same patient, adipose tissue (AT) depots through proteomic profile expression analyses. Serum and AT samples from subcutaneous (SAT) and visceral (VAT) fat were collected during bariatric surgery. Bead-based targeted multiplex assay systems were used to simultaneously detect and quantify multiple targets in serum samples (targeted proteomics) and analyze changes in adipokine serum composition. AT samples were assessed through an untargeted proteomics approach. Through a systems biology analysis of the proteomic data, information on the affected biological pathways was acquired. In obese class III individuals, the presence of T2DM induced a significantly higher systemic release of ghrelin, GLP-1, glucagon, MMP3, BAFF, chitinase 3-like 1, TNF-R1 and TNF-R2, and a lower systemic release of IL-8. SAT and VAT proteomes belonging to the same patient showed significant differences in local protein content. While the proteins upregulated in VAT were indicative of metabolic dysregulation, SAT protein upregulation suggested adequate endocrine regulation. The presence of T2DM significantly affected VAT protein composition through the upregulation of dysregulating metabolic pathways, but SAT protein composition was not significantly modified. Our results show that T2DM induces metabolic dysregulation in obese individuals with changes in systemic marker levels and impairment of proteostasis in VAT but not in SAT. Keywords: visceral adipose tissue; subcutaneous adipose tissue; diabetes; proteomic analysis Author: Gemma Arderiu, Guiomar Mendieta, Alex Gallinat, Carmen Lambert, Alberto Díez-Caballero, Carlos Ballesta and Lina Badimon Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Jan 6 10:45:57 2023 CET ModDate: Fri Jan 6 11:41:33 2023 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 22768517 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 TLGRFU+VnURWPalladioL Type 1 Custom yes yes no 15 0 VEBTKK+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 ZWDBVF+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 QDENQE+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 46 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 KXDJCR+CMSY10 Type 1 Builtin yes yes no 75 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 100 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 108 0 IHLKJH+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 140 0 IHLKJJ+PalatinoLinotype TrueType WinAnsi yes yes no 143 0 IHLKJL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 146 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-12-06 02:45:21 CET RepresentationInformation: 303862.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-12-05 11:47:37 CET Size: 22768517 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 396 FreeObjects: 11 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Influence of Type 2 Diabetes on Serum Proteins of Obese Individuals Destination: subsection.2.1 Item: Title: Differential Protein Expression between Subcutaneous and Visceral White Adipose Tissue Destination: subsection.2.2 Item: Title: Type 2 Diabetes and Obesity: Effects on the Proteome of Visceral and Subcutaneous Adipose Tissue Destination: subsection.2.3 Item: Title: Effect of White Adipose Tissue Proteome Composition upon Serum Adipokine Signature Destination: subsection.2.4 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Study Population Destination: subsection.4.1 Item: Title: Sample Collection Destination: subsection.4.2 Item: Title: Biochemical Analysis Destination: subsection.4.3 Item: Title: Two-Dimensional Gel Electrophoresis (2-DE) Destination: subsection.4.4 Item: Title: Western Blot Analysis Destination: subsection.4.5 Item: Title: Mass Spectrometry Analysis Destination: subsection.4.6 Item: Title: Quantification of Serum Protein Levels Destination: subsection.4.7 Item: Title: In Silico Analysis Destination: subsection.4.8 Item: Title: Statistical Analysis Destination: subsection.4.9 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles Author: Gemma Arderiu, Guiomar Mendieta, Alex Gallinat, Carmen Lambert, Alberto Díez-Caballero, Carlos Ballesta and Lina Badimon Subject: Obesity is associated with metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM), further increasing an already heightened cardiovascular risk. Here, amongst obese class III bariatric surgery patients, we have investigated the effect of T2DM in serum and in two, same patient, adipose tissue (AT) depots through proteomic profile expression analyses. Serum and AT samples from subcutaneous (SAT) and visceral (VAT) fat were collected during bariatric surgery. Bead-based targeted multiplex assay systems were used to simultaneously detect and quantify multiple targets in serum samples (targeted proteomics) and analyze changes in adipokine serum composition. AT samples were assessed through an untargeted proteomics approach. Through a systems biology analysis of the proteomic data, information on the affected biological pathways was acquired. In obese class III individuals, the presence of T2DM induced a significantly higher systemic release of ghrelin, GLP-1, glucagon, MMP3, BAFF, chitinase 3-like 1, TNF-R1 and TNF-R2, and a lower systemic release of IL-8. SAT and VAT proteomes belonging to the same patient showed significant differences in local protein content. While the proteins upregulated in VAT were indicative of metabolic dysregulation, SAT protein upregulation suggested adequate endocrine regulation. The presence of T2DM significantly affected VAT protein composition through the upregulation of dysregulating metabolic pathways, but SAT protein composition was not significantly modified. Our results show that T2DM induces metabolic dysregulation in obese individuals with changes in systemic marker levels and impairment of proteostasis in VAT but not in SAT. 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