Sökning: onr:"swepub:oai:DiVA.org:oru-63701" >
Increased dihydroce...
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Barbarroja, NuriaMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Instituto Maimónides de Investigación Biomédica de Córdoba, Reina Sofia University Hospital, Córdoba, Spain
(författare)
Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function
- Artikel/kapitelEngelska2015
Förlag, utgivningsår, omfång ...
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2014-10-28
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American Diabetes Association,2015
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:oru-63701
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-63701URI
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https://doi.org/10.2337/db14-0359DOI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding agencies:Medical Research Council (MRC)Metabolic Diseases Unit of the MRCBritish Heart Foundation
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Rodriguez-Cuenca, SergioMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
(författare)
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Nygren, HeliVTT Technical Research Centre of Finland, Espoo, Finland
(författare)
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Camargo, AntonioMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Lipids and Atherosclerosis Research Unit, Instituto Maimónides de Investigación Biomédica de Córdoba, Reina Sofia University Hospital, Córdoba, Spain
(författare)
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Pirraco, AnaMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal
(författare)
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Relat, JoanaDepartament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain
(författare)
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Cuadrado, IreneDepartamento de Farmacología, Universidad Complutense de Madrid, Madrid, Spain
(författare)
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Pellegrinelli, VanessaMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
(författare)
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Medina-Gomez, GemaMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
(författare)
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Lopez-Pedrera, CharyInstituto Maimónides de Investigación Biomédica de Córdoba, Reina Sofia University Hospital, Córdoba, Spain
(författare)
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Tinahones, Francisco J.CIBER in Physiopathology of Obesity and Nutrition (CB06/03), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación Biomédica de Málaga, Hospital Virgen de la Victoria, Malaga, Spain
(författare)
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Symons, J. DavidCollege of Health, University of Utah, Salt Lake City UT, United States; Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City UT, United States
(författare)
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Summers, Scott A.Program in Cardiovascular and Metabolic Disorders, Duke-National University, Singapore Graduate Medical School, Singapore, Singapore
(författare)
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Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center, Gentofte, Denmark(Swepub:oru)moc
(författare)
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Vidal-Puig, AntonioMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, United Kingdom
(författare)
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Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Instituto Maimónides de Investigación Biomédica de Córdoba, Reina Sofia University Hospital, Córdoba, SpainMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Diabetes: American Diabetes Association64:4, s. 1180-11920012-17971939-327X
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Diabetes
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Barbarroja, Nuri ...
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Rodriguez-Cuenca ...
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Nygren, Heli
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Camargo, Antonio
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Pirraco, Ana
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Relat, Joana
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visa fler...
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Cuadrado, Irene
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Pellegrinelli, V ...
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Medina-Gomez, Ge ...
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Lopez-Pedrera, C ...
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Tinahones, Franc ...
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Symons, J. David
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Summers, Scott A ...
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Oresic, Matej, 1 ...
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Vidal-Puig, Anto ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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Diabetes
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Örebro universitet