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The occurrence of comorbidities is associated with systemic and adipose tissue inflammation, which is marked by the presence of macrophages and neutrophils in adipose tissue. The role of neutrophils in driving adipose tissue inflammation and pathology is understudied and may hold therapeutic promise.\n                    <jats:italic>\n                      MRP8\n                      <jats:sup>Cre<\/jats:sup>\n                    <\/jats:italic>\n                    transgenic mice are frequently used to investigate neutrophil functions. A recent report demonstrates that the insertion of the\n                    <jats:italic>\n                      MRP8\n                      <jats:sup>Cre<\/jats:sup>\n                    <\/jats:italic>\n                    transgene resulted in whole\u2010body deletion of\n                    <jats:italic>Ap1s1<\/jats:italic>\n                    and\n                    <jats:italic>Serpine1<\/jats:italic>\n                    , the latter encoding the pro\u2010obesogenic factor plasminogen activator inhibitor\u20101 (PAI\u20101). Here, we show that\n                    <jats:italic>\n                      MRP8\n                      <jats:sup>Cre<\/jats:sup>\n                    <\/jats:italic>\n                    transgenic mice have lower body weight than their littermate controls on a standard chow diet. Furthermore, they are resistant to weight gain, adipose tissue hypertrophy, systemic deregulation of glucose metabolism, infiltration of macrophages into AT, and liver steatosis upon feeding of obesogenic, high\u2010fat diets (HFD). Mechanistically, this was independent of neutrophils or bone marrow\u2010derived cells, sex, age of the mice, the duration of the HFD feeding, treatment start, housing facility, or the original source of the mice. The expression of\n                    <jats:italic>Sepine1<\/jats:italic>\n                    \/PAI\u20101 and\n                    <jats:italic>Ap1s1<\/jats:italic>\n                    is globally reduced across metabolic organs of\n                    <jats:italic>\n                      MRP8\n                      <jats:sup>Cre<\/jats:sup>\n                    <\/jats:italic>\n                    mice irrespective of diet, thus phenocopying previous reports of the obesity\u2010protective effect of PAI\u20101 depletion in mice. Our findings demonstrate the limited applicability of\n                    <jats:italic>\n                      MRP8\n                      <jats:sup>Cre<\/jats:sup>\n                    <\/jats:italic>\n                    mice for obesity or metabolic studies due to the observed off\u2010target effects and highlight the need for respective controls when using transgenic mice, such as Cre\u2010only controls or use of independent Cre lines for studies involving the Cre\/\n                    <jats:italic>loxP<\/jats:italic>\n                    system.\n                  <\/jats:p>","DOI":"10.1002\/eji.70271","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:19:01Z","timestamp":1789543141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>MRP8\u2010Cre<\/i>\n                    Transgenic Mice Are Resistant to Weight Gain and Diet\u2010Induced Obesity Independently of Neutrophils"],"prefix":"10.1002","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2680-8097","authenticated-orcid":false,"given":"Stephan","family":"Forisch","sequence":"first","affiliation":[{"name":"Innate Immune Biology Laboratory Institute For Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST)  Barcelona Spain"},{"name":"Programa de Doctorat en Biomedicina Universitat De Barcelona (UB) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9280-3058","authenticated-orcid":false,"given":"Fatemeh","family":"Soltani","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences (Division of Experimental Medicine) McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3028-9119","authenticated-orcid":false,"given":"Laia","family":"Salvat Costa","sequence":"additional","affiliation":[{"name":"Innate Immune Biology Laboratory Institute For Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST)  Barcelona Spain"},{"name":"Programa de Doctorat en Biomedicina Universitat De Barcelona (UB) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2357-6681","authenticated-orcid":false,"given":"Beatriz","family":"M. Cardoso","sequence":"additional","affiliation":[{"name":"Innate Immune Biology Laboratory Institute For Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9862-4978","authenticated-orcid":false,"given":"Yaiza","family":"Moreno Galiano","sequence":"additional","affiliation":[{"name":"Innate Immune Biology Laboratory Institute For Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4870-6542","authenticated-orcid":false,"given":"Cedric","family":"Duval","sequence":"additional","affiliation":[{"name":"Leeds Thrombosis Collective, Discovery &amp; Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6310-5745","authenticated-orcid":false,"given":"Robert A. 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