{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:42:20Z","timestamp":1790109740662,"version":"4.0.1"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hamad Medical Corporation","award":["#16245\/16"],"award-info":[{"award-number":["#16245\/16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity is commonly associated with metabolic diseases including type 2 diabetes, hypertension, and dyslipidemia. Moreover, individuals with obesity are at increased risk of cardiovascular disease. However, a subgroup of individuals within the obese population presents without concurrent metabolic disorders. Even though this group has a stable metabolic status and does not exhibit overt metabolic disease, this status may be transient; these individuals may have subclinical metabolic derangements. To investigate the latter hypothesis, an analysis of the proteome signature was conducted. Plasma samples from 27 subjects with obesity but without an associated metabolic disorder (obesity only (OBO)) and 15 lean healthy control (LHC) subjects were examined. Fasting samples were subjected to Olink proteomics analysis targeting 184 proteins enriched in cardiometabolic and inflammation pathways. Our results distinctly delineated two groups with distinct plasma protein expression profiles. Specifically, a total of 24 proteins were differentially expressed in individuals with obesity compared to LHC. Among these, 13 proteins were downregulated, whereas 11 proteins were upregulated. The pathways that were upregulated in the OBO group were related to chemoattractant activity, growth factor activity, G protein-coupled receptor binding, chemokine activity, and cytokine activity, whereas the pathways that were downregulated include regulation of T cell differentiation, leukocyte differentiation, reproductive system development, inflammatory response, neutrophil, lymphocyte, monocyte and leukocyte chemotaxis, and neutrophil migration. The study identifies several pathways that are altered in individuals with obesity compared to healthy control subjects. These findings provide valuable insights into the underlying mechanisms, potentially paving the way for the identification of therapeutic targets aimed at improving metabolic health in individuals with obesity.<\/jats:p>","DOI":"10.3390\/ijms26052262","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T03:26:21Z","timestamp":1741058781000},"page":"2262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolically Healthy Obesity Is Characterized by a Distinct Proteome Signature"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1104-0852","authenticated-orcid":false,"given":"Fayaz Ahmad","family":"Mir","sequence":"first","affiliation":[{"name":"Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"},{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6886-6036","authenticated-orcid":false,"given":"Houari B.","family":"Abdesselem","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhan","family":"Cyprian","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Iskandarani","sequence":"additional","affiliation":[{"name":"Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmma","family":"Doudin","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, Research Department, Sidra Medicine, Doha P.O. Box 26999, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutasem AbdelRahim","family":"Shraim","sequence":"additional","affiliation":[{"name":"Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4113-4391","authenticated-orcid":false,"given":"Bader M.","family":"Alkhalaf","sequence":"additional","affiliation":[{"name":"Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0965-6455","authenticated-orcid":false,"given":"Meis","family":"Alkasem","sequence":"additional","affiliation":[{"name":"Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8063-1117","authenticated-orcid":false,"given":"Ibrahem","family":"Abdalhakam","sequence":"additional","affiliation":[{"name":"Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilham","family":"Bensmail","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1422-4507","authenticated-orcid":false,"given":"Hamza A.","family":"Al Halabi","sequence":"additional","affiliation":[{"name":"Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8314-1500","authenticated-orcid":false,"given":"Shahrad","family":"Taheri","sequence":"additional","affiliation":[{"name":"Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"},{"name":"National Obesity Treatment Center, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"},{"name":"Weil Cornell Medicine\u2014Qatar, Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul-Badi","family":"Abou-Samra","sequence":"additional","affiliation":[{"name":"Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"},{"name":"National Obesity Treatment Center, Hamad Medical Corporation, Doha P.O. Box 3010, Qatar"},{"name":"Weil Cornell Medicine\u2014Qatar, Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"ref_1","unstructured":"World Obesity Federation (2023). World Obesity Altas, World Obesity Federation."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Neto, A., Fernandes, A., and Barateiro, A. (2023). The complex relationship between obesity and neurodegenerative diseases: An updated review. Front. Cell. 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