PMID- 36614270 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20230111 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 1 DP - 2023 Jan 3 TI - Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles. LID - 10.3390/ijms24010827 [doi] LID - 827 AB - 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. FAU - Arderiu, Gemma AU - Arderiu G AD - Cardiovascular-Program, Institut d'Investigacio Biomedica Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CiberCV), 28029 Barcelona, Spain. FAU - Mendieta, Guiomar AU - Mendieta G AD - Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain. FAU - Gallinat, Alex AU - Gallinat A AUID- ORCID: 0000-0002-1521-2175 AD - Cardiovascular-Program, Institut d'Investigacio Biomedica Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain. FAU - Lambert, Carmen AU - Lambert C AUID- ORCID: 0000-0002-7929-4990 AD - Cardiovascular-Program, Institut d'Investigacio Biomedica Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain. AD - IPSA-Instituto de Investigacion Sanitaria del Principado de Asturias, 33011 Oviedo, Spain. FAU - Diez-Caballero, Alberto AU - Diez-Caballero A AD - Centro Medico Teknon, Grupo Quiron Salut, 08022 Barcelona, Spain. FAU - Ballesta, Carlos AU - Ballesta C AD - Centro Medico Teknon, Grupo Quiron Salut, 08022 Barcelona, Spain. FAU - Badimon, Lina AU - Badimon L AUID- ORCID: 0000-0002-9162-2459 AD - Cardiovascular-Program, Institut d'Investigacio Biomedica Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CiberCV), 28029 Barcelona, Spain. LA - eng GR - PID2019-107160RB-100/Plan National Proyectos Investigacion y Desarrollo/ GR - CIBERCV-CB16/11/00411/Centro de Investigacion Biomedica en Red Cardiovascular/ GR - PI20/01517/Institute of Health Carlos III (ISCIII)/ GR - 2017 SGR 1480/Secretaria d'Universitats i Recerca, Departament d'Economia i Coneixement/ PT - Journal Article DEP - 20230103 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/metabolism MH - Subcutaneous Fat/metabolism MH - Proteomics MH - Systems Biology MH - Obesity/metabolism MH - Adipose Tissue/metabolism MH - Intra-Abdominal Fat/metabolism PMC - PMC9821208 OTO - NOTNLM OT - diabetes OT - proteomic analysis OT - subcutaneous adipose tissue OT - visceral adipose tissue COIS- L.B. declares to have acted as a SAB member of Sanofi, Ionnis, Pfizer and NovoNordisk; to have a Research Grant from AstraZeneca; to have received speaker fees from Sanofi and Bayer and to have founded the Spin-offs Glycardial Diagnostics SL and Ivastatin Therapeutics S (all unrelated to this work). The remaining authors have nothing to disclose. The authors declare no conflict of interest. EDAT- 2023/01/09 06:00 MHDA- 2023/01/11 06:00 PMCR- 2023/01/03 CRDT- 2023/01/08 01:26 PHST- 2022/11/22 00:00 [received] PHST- 2022/12/16 00:00 [revised] PHST- 2022/12/22 00:00 [accepted] PHST- 2023/01/08 01:26 [entrez] PHST- 2023/01/09 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2023/01/03 00:00 [pmc-release] AID - ijms24010827 [pii] AID - ijms-24-00827 [pii] AID - 10.3390/ijms24010827 [doi] PST - epublish SO - Int J Mol Sci. 2023 Jan 3;24(1):827. doi: 10.3390/ijms24010827.