Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles

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 pat...

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Main Authors: Gemma Arderiu, Guiomar Mendieta, Alex Gallinat, Carmen Lambert, Alberto Díez-Caballero, Carlos Ballesta, Lina Badimon
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/1/827
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author Gemma Arderiu
Guiomar Mendieta
Alex Gallinat
Carmen Lambert
Alberto Díez-Caballero
Carlos Ballesta
Lina Badimon
author_facet Gemma Arderiu
Guiomar Mendieta
Alex Gallinat
Carmen Lambert
Alberto Díez-Caballero
Carlos Ballesta
Lina Badimon
author_sort Gemma Arderiu
collection DOAJ
description 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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spelling doaj.art-6aa0f79401ce4b63a03378495127db322023-11-16T15:39:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124182710.3390/ijms24010827Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic ProfilesGemma Arderiu0Guiomar Mendieta1Alex Gallinat2Carmen Lambert3Alberto Díez-Caballero4Carlos Ballesta5Lina Badimon6Cardiovascular-Program, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainCentro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, SpainCardiovascular-Program, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainCardiovascular-Program, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainCentro Médico Teknon, Grupo Quiron Salut, 08022 Barcelona, SpainCentro Médico Teknon, Grupo Quiron Salut, 08022 Barcelona, SpainCardiovascular-Program, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainObesity 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.https://www.mdpi.com/1422-0067/24/1/827visceral adipose tissuesubcutaneous adipose tissuediabetesproteomic analysis
spellingShingle Gemma Arderiu
Guiomar Mendieta
Alex Gallinat
Carmen Lambert
Alberto Díez-Caballero
Carlos Ballesta
Lina Badimon
Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles
International Journal of Molecular Sciences
visceral adipose tissue
subcutaneous adipose tissue
diabetes
proteomic analysis
title Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles
title_full Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles
title_fullStr Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles
title_full_unstemmed Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles
title_short Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles
title_sort type 2 diabetes in obesity a systems biology study on serum and adipose tissue proteomic profiles
topic visceral adipose tissue
subcutaneous adipose tissue
diabetes
proteomic analysis
url https://www.mdpi.com/1422-0067/24/1/827
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