{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:32:50Z","timestamp":1773801170628,"version":"3.50.1"},"reference-count":27,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":338,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7-ETHERPATHS"],"award-info":[{"award-number":["FP7-ETHERPATHS"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MDU MRC"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,4,1]]},"abstract":"<jats:p>Adipose tissue dysfunction is an important determinant of obesity-associated, lipid-induced metabolic complications. Ceramides are well-known mediators of lipid-induced insulin resistance in peripheral organs such as muscle. DEGS1 is the desaturase catalyzing the last step in the main ceramide biosynthetic pathway. Functional suppression of DEGS1 activity results in substantial changes in ceramide species likely to affect fundamental biological functions such as oxidative stress, cell survival, and proliferation. Here, we show that degs1 expression is specifically decreased in the adipose tissue of obese patients and murine models of genetic and nutritional obesity. Moreover, loss-of-function experiments using pharmacological or genetic ablation of DEGS1 in preadipocytes prevented adipogenesis and decreased lipid accumulation. This was associated with elevated oxidative stress, cellular death, and blockage of the cell cycle. These effects were coupled with increased dihydroceramide content. Finally, we validated in vivo that pharmacological inhibition of DEGS1 impairs adipocyte differentiation. These data identify DEGS1 as a new potential target to restore adipose tissue function and prevent obesity-associated metabolic disturbances.<\/jats:p>","DOI":"10.2337\/db14-0359","type":"journal-article","created":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T06:33:21Z","timestamp":1414564401000},"page":"1180-1192","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":62,"title":["Increased Dihydroceramide\/Ceramide Ratio Mediated by Defective Expression of <i>degs1<\/i> Impairs Adipocyte Differentiation and Function"],"prefix":"10.2337","volume":"64","author":[{"given":"Nuria","family":"Barbarroja","sequence":"first","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K."},{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Reina Sofia University Hospital, C\u00f3rdoba, Spain"}]},{"given":"Sergio","family":"Rodriguez-Cuenca","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K."}]},{"given":"Heli","family":"Nygren","sequence":"additional","affiliation":[{"name":"VTT Technical Research Centre of Finland, Espoo, Finland"}]},{"given":"Antonio","family":"Camargo","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K."},{"name":"Lipids and Atherosclerosis Research Unit, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Reina Sofia University Hospital, C\u00f3rdoba, Spain"}]},{"given":"Ana","family":"Pirraco","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K."},{"name":"Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Joana","family":"Relat","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain"}]},{"given":"Irene","family":"Cuadrado","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Universidad Complutense de Madrid, Madrid, Spain"}]},{"given":"Vanessa","family":"Pellegrinelli","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K."}]},{"given":"Gema","family":"Medina-Gomez","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K."}]},{"given":"Chary","family":"Lopez-Pedrera","sequence":"additional","affiliation":[{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Reina Sofia University Hospital, C\u00f3rdoba, Spain"}]},{"given":"Francisco J.","family":"Tinahones","sequence":"additional","affiliation":[{"name":"CIBER in Physiopathology of Obesity and Nutrition (CB06\/03), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga\/Hospital Virgen de la Victoria, Malaga, Spain"}]},{"given":"J. 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