{"entity": "researcher", "timestamp": "2026-08-22T06:58:04.735Z", "family": "Vidal-Puig", "given": "Antonio", "initials": "A", "orcid": "0000-0003-4220-9577", "affiliations": ["Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.", "University of Cambridge Metabolic Research Laboratories, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bc1d6ef9608423590d957229bac97f3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bc1d6ef9608423590d957229bac97f3"}}, "publications": [{"entity": "publication", "iuid": "1cf307e6f1cb4c5196e9f32d704f7a9d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1cf307e6f1cb4c5196e9f32d704f7a9d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1cf307e6f1cb4c5196e9f32d704f7a9d"}}, "title": "Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance.", "authors": [{"family": "Pellegrinelli", "given": "V", "initials": "V", "orcid": "0000-0002-2055-4321", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d1b31e1d74a14aaeb205211bbb7a6540.json"}}, {"family": "Rodriguez-Cuenca", "given": "S", "initials": "S"}, {"family": "Rouault", "given": "C", "initials": "C"}, {"family": "Figueroa-Juarez", "given": "E", "initials": "E", "orcid": "0000-0002-5634-7682", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/40dd51ee16da4d9286ef47c9525cb7e5.json"}}, {"family": "Schilbert", "given": "H", "initials": "H", "orcid": "0000-0003-0474-7753", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c895ab9bedb4aa1bd192c3a8bdd13f4.json"}}, {"family": "Virtue", "given": "S", "initials": "S", "orcid": "0000-0002-9545-5432", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f89119be7414f3292c576fa2394b5a5.json"}}, {"family": "Moreno-Navarrete", "given": "J M", "initials": "JM", "orcid": "0000-0002-2883-511X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f81d0e5d110f4c27b8363bee3088239b.json"}}, {"family": "Bidault", "given": "G", "initials": "G", "orcid": "0000-0002-8396-9962", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e13f6e97aad04d34a5838a219c7e8085.json"}}, {"family": "V\u00e1zquez-Borrego", "given": "M C", "initials": "MC"}, {"family": "Dias", "given": "A R", "initials": "AR", "orcid": "0000-0002-0679-031X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c905fa9a80344d9ad0b419890433827.json"}}, {"family": "Pucker", "given": "B", "initials": "B", "orcid": "0000-0002-3321-7471", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/89263a44edd34f86a6290829f648ff96.json"}}, {"family": "Dale", "given": "M", "initials": "M"}, {"family": "Campbell", "given": "M", "initials": "M"}, {"family": "Carobbio", "given": "S", "initials": "S", "orcid": "0000-0001-6631-7930", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3e8440775dca4445b41ccfa7e29de877.json"}}, {"family": "Lin", "given": "Y H", "initials": "YH", "orcid": "0000-0002-4609-145X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/508e639a2317433abc5a8fa96e50198c.json"}}, {"family": "Vacca", "given": "M", "initials": "M", "orcid": "0000-0002-1973-224X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2d380abac54e4a9793460008007e8d96.json"}}, {"family": "Aron-Wisnewsky", "given": "J", "initials": "J"}, {"family": "Mora", "given": "S", "initials": "S"}, {"family": "Masiero", "given": "M M", "initials": "MM"}, {"family": "Emmanouilidou", "given": "A", "initials": "A"}, {"family": "Mukhopadhyay", "given": "S", "initials": "S", "orcid": "0000-0002-7110-6473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea054e42a2cf42d28db985fadff22fd5.json"}}, {"family": "Dougan", "given": "G", "initials": "G"}, {"family": "den Hoed", "given": "M", "initials": "M", "orcid": "0000-0001-8081-428X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d3e34c06cff4446ad703cde901c5033.json"}}, {"family": "Loos", "given": "R J F", "initials": "RJF", "orcid": "0000-0002-8532-5087", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/179eb6511eba4d33b633599c5652e344.json"}}, {"family": "Fern\u00e1ndez-Real", "given": "J M", "initials": "JM"}, {"family": "Chiarugi", "given": "D", "initials": "D"}, {"family": "Cl\u00e9ment", "given": "K", "initials": "K", "orcid": "0000-0002-2489-3355", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/af0ccf770379432992af080f98ef499b.json"}}, {"family": "Vidal-Puig", "given": "A", "initials": "A", "orcid": "0000-0003-4220-9577", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bc1d6ef9608423590d957229bac97f3.json"}}], "type": "journal article", "published": "2022-04-00", "journal": {"title": "Nat Metab", "issn": "2522-5812", "volume": "4", "issue": "4", "pages": "476-494", "issn-l": "2522-5812"}, "abstract": "Resulting from impaired collagen turnover, fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance (IR). Prolidase, also known as peptidase D (PEPD), plays a vital role in collagen turnover by degrading proline-containing dipeptides but its specific functional relevance in AT is unknown. Here we show that in human and mouse obesity, PEPD expression and activity decrease in AT, and PEPD is released into the systemic circulation, which promotes fibrosis and AT IR. Loss of the enzymatic function of PEPD by genetic ablation or pharmacological inhibition causes AT fibrosis in mice. In addition to its intracellular enzymatic role, secreted extracellular PEPD protein enhances macrophage and adipocyte fibro-inflammatory responses via EGFR signalling, thereby promoting AT fibrosis and IR. We further show that decreased prolidase activity is coupled with increased systemic levels of PEPD that act as a pathogenic trigger of AT fibrosis and IR. Thus, PEPD produced by macrophages might serve as a biomarker of AT fibro-inflammation and could represent a therapeutic target for AT fibrosis and obesity-associated IR and type 2 diabetes.", "doi": "10.1038/s42255-022-00561-5", "pmid": "35478031", "labels": [], "xrefs": [{"db": "mid", "key": "EMS143944"}, {"db": "pmc", "key": "PMC7617220"}, {"db": "pii", "key": "10.1038/s42255-022-00561-5"}], "notes": [], "created": "2026-08-21T11:54:46.613Z", "modified": "2026-08-21T11:54:47.144Z"}, {"entity": "publication", "iuid": "7a90a12bc74a4bc383569d5ce4b5f4ec", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7a90a12bc74a4bc383569d5ce4b5f4ec.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7a90a12bc74a4bc383569d5ce4b5f4ec"}}, "title": "Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities.", "authors": [{"family": "Huang", "given": "Lam O", "initials": "LO", "orcid": "0000-0001-7592-0942", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cd155f0effb0459097e1f006065586af.json"}}, {"family": "Rauch", "given": "Alexander", "initials": "A", "orcid": "0000-0002-9429-7356", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d40267b2a564e1da085877bd09508e0.json"}}, {"family": "Mazzaferro", "given": "Eugenia", "initials": "E"}, {"family": "Preuss", "given": "Michael", "initials": "M", "orcid": "0000-0001-5266-8465", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d0525e8578f74066a0c3204e121c629d.json"}}, {"family": "Carobbio", "given": "Stefania", "initials": "S"}, {"family": "Bayrak", "given": "Cigdem S", "initials": "CS", "orcid": "0000-0002-3883-5535", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/283fc2f0cc674c0c9ff4dddc9bc086f5.json"}}, {"family": "Chami", "given": "Nathalie", "initials": "N", "orcid": "0000-0002-8547-6424", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cffb582bc9704ff483e1081ffaf46adb.json"}}, {"family": "Wang", "given": "Zhe", "initials": "Z", "orcid": "0000-0002-8046-4969", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f925d8ce81524036b0566ce2990b55bc.json"}}, {"family": "Schick", "given": "Ursula M", "initials": "UM"}, {"family": "Yang", "given": "Nancy", "initials": "N"}, {"family": "Itan", "given": "Yuval", "initials": "Y"}, {"family": "Vidal-Puig", "given": "Antonio", "initials": "A", "orcid": "0000-0003-4220-9577", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8bc1d6ef9608423590d957229bac97f3.json"}}, {"family": "den Hoed", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8081-428X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d3e34c06cff4446ad703cde901c5033.json"}}, {"family": "Mandrup", "given": "Susanne", "initials": "S", "orcid": "0000-0002-0961-5787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385b86cd99b944b9b9a250d94dc48899.json"}}, {"family": "Kilpel\u00e4inen", "given": "Tuomas O", "initials": "TO", "orcid": "0000-0002-8349-3028", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/47a391523ed6449d9cd9fef22897789c.json"}}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF", "orcid": "0000-0002-8532-5087", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/179eb6511eba4d33b633599c5652e344.json"}}], "type": "journal article", "published": "2021-02-00", "journal": {"title": "Nat Metab", "issn": "2522-5812", "volume": "3", "issue": "2", "pages": "228-243", "issn-l": "2522-5812"}, "abstract": "Obesity is a major risk factor for cardiometabolic diseases. Nevertheless, a substantial proportion of individuals with obesity do not suffer cardiometabolic comorbidities. The mechanisms that uncouple adiposity from its cardiometabolic complications are not fully understood. Here, we identify 62 loci of which the same allele is significantly associated with both higher adiposity and lower cardiometabolic risk. Functional analyses show that the 62 loci are enriched for genes expressed in adipose tissue, and for regulatory variants that influence nearby genes that affect adipocyte differentiation. Genes prioritized in each locus support a key role of fat distribution (FAM13A, IRS1 and PPARG) and adipocyte function (ALDH2, CCDC92, DNAH10, ESR1, FAM13A, MTOR, PIK3R1 and VEGFB). Several additional mechanisms are involved as well, such as insulin-glucose signalling (ADCY5, ARAP1, CREBBP, FAM13A, MTOR, PEPD, RAC1 and SH2B3), energy expenditure and fatty acid oxidation (IGF2BP2), browning of white adipose tissue (CSK, VEGFA, VEGFB and SLC22A3) and inflammation (SH2B3, DAGLB and ADCY9). Some of these genes may represent therapeutic targets to reduce cardiometabolic risk linked to excess adiposity.", "doi": "10.1038/s42255-021-00346-2", "pmid": "33619380", "labels": [], "xrefs": [{"db": "pii", "key": "10.1038/s42255-021-00346-2"}], "notes": [], "created": "2026-08-21T11:54:44.205Z", "modified": "2026-08-21T11:54:44.452Z"}]}