{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:15:49Z","timestamp":1768810549063,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030\u2010179344"],"award-info":[{"award-number":["310030\u2010179344"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030\u2010215451"],"award-info":[{"award-number":["310030\u2010215451"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001835","name":"Universiteit Maastricht","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001835","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000855","name":"University of Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["209933838"],"award-info":[{"award-number":["209933838"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adipocyte\u2010specific Fas knockout (Fas<jats:sup>\u0394adipo<\/jats:sup>) and control littermate (Fas<jats:sup>F\/F<\/jats:sup>) mice were fed a regular chow diet or a high\u2010fat diet (HFD) for 20\u2009weeks. Energy expenditure was assessed by indirect calorimetry, and browning was determined in subcutaneous WAT. In vitro, UCP1 was analyzed in subcutaneous murine adipocytes treated with or without Fas ligand. Moreover, <jats:italic>FAS<\/jats:italic> expression in WAT was correlated to <jats:italic>UCP1<\/jats:italic> and percentage of body fat in human individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HFD\u2010fed Fas<jats:sup>\u0394adipo<\/jats:sup> mice displayed reduced body weight gain and blunted adiposity compared to control littermates. Concomitantly, whole\u2010body energy expenditure and WAT browning were elevated. In cultured adipocytes, Fas ligand treatment blunted isoproterenol\u2010induced UCP1 protein levels. In support of these findings in rodents, <jats:italic>FAS<\/jats:italic> expression in WAT correlated negatively with <jats:italic>UCP1<\/jats:italic> but positively with adiposity in human individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Fas activation in adipocytes contributes to HFD\u2010associated adiposity in rodents and may be a therapeutic target to reduce obesity and associated diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.24092","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:20:23Z","timestamp":1721262023000},"page":"1812-1818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fas (<scp>CD95<\/scp>) expression in adipocytes contributes to diet\u2010induced obesity"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0176-8906","authenticated-orcid":false,"given":"Stephan","family":"Wueest","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich  Zurich Switzerland"},{"name":"Children's Research Center University Children's Hospital, University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Scaffidi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich  Zurich Switzerland"},{"name":"Children's Research Center University Children's Hospital, University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pim P.","family":"van Krieken","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich  Zurich Switzerland"},{"name":"Children's Research Center University Children's Hospital, University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils K.","family":"Konrad","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich  Zurich Switzerland"},{"name":"Children's Research Center University Children's Hospital, University of Zurich  Zurich Switzerland"},{"name":"Department of Medical Oncology and Hematology University of Zurich and University Hospital Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology University of Zurich and University Hospital Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S. F.","family":"Wiedemann","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich  Zurich Switzerland"},{"name":"Children's Research Center University Children's Hospital, University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Goergen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich  Zurich Switzerland"},{"name":"Children's Research Center University Children's Hospital, University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Borsigova","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich  Zurich Switzerland"},{"name":"Children's Research Center University Children's Hospital, University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis G.","family":"Lempesis","sequence":"additional","affiliation":[{"name":"Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Center<sup>+<\/sup>  Maastricht The Netherlands"},{"name":"Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences University of Birmingham  Birmingham UK"},{"name":"Centre for Endocrinology, Diabetes and Metabolism Birmingham Health Partners  Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Fullin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology University of Zurich and University Hospital Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos 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