{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:30:23Z","timestamp":1790746223562,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006678","name":"Association Fran\u00e7aise pour l'Etude du Foie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006678","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008765","name":"Soci\u00e9t\u00e9 Nationale Fran\u00e7aise de Gastro-Ent\u00e9rologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008765","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study investigated the contribution of osteopontin\/secreted phosphoprotein 1 (SPP1) to T\u2010cell regulation in initiation of obesity\u2010driven adipose tissue (AT) inflammation and macrophage infiltration and the subsequent impact on insulin resistance (IR) and metabolic\u2010associated fatty liver disease (MAFLD) development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SPP1 and T\u2010cell marker expression was evaluated in AT and liver according to type 2 diabetes and MAFLD in human individuals\u00a0with obesity. The role of SPP1 on T cells was evaluated in <jats:italic>Spp1<\/jats:italic>\u2010knockout mice challenged with a high\u2010fat diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In humans\u00a0with obesity, elevated SPP1 expression in AT was parallel to T\u2010cell marker expression (CD4, CD8A) and IR. Weight loss reversed AT inflammation with decreased SPP1 and CD8A expression. In liver, elevated SPP1 expression correlated with MAFLD severity and hepatic T\u2010cell markers. In mice, although <jats:italic>Spp1<\/jats:italic> deficiency did not impact obesity, it did improve AT IR associated with prevention of proinflammatory T\u2010cell accumulation at the expense of regulatory T cells. <jats:italic>Spp1<\/jats:italic> deficiency also decreased <jats:italic>ex vivo<\/jats:italic> helper T cell, subtype 1 (Th1)\u00a0polarization of AT CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells. In addition, <jats:italic>Spp1<\/jats:italic> deficiency significantly reduced obesity\u2010associated liver steatosis and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Current findings highlight a critical role of SPP1 in the initiation of obesity\u2010driven chronic inflammation by regulating accumulation and\/or polarization of T cells. Early targeting of SPP1 could be beneficial for IR and MAFLD treatment.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/oby23868-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.23868","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T07:27:11Z","timestamp":1695108431000},"page":"2568-2582","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Osteopontin\u2010driven T\u2010cell accumulation and function in adipose tissue and liver promoted insulin resistance and <scp>MAFLD<\/scp>"],"prefix":"10.1002","volume":"31","author":[{"given":"Fr\u00e9d\u00e9ric","family":"Soysouvanh","sequence":"first","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, INSERM, U1065, C3M  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9borah","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, INSERM, U1065, C3M  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Bonnafous","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, CHU, INSERM, U1065, C3M  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Bourinet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, INSERM, U1065, C3M  Nice 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