Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/166517
Title: Increased Dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function.
Author: Barbarroja, Nuria
Rodriguez Cuenca, Sergio
Nygren, Heli
Camargo, Antonio
Pirraco, Ana
Relat Pardo, Joana
Cuadrado, Irene
Pellegrinelli, Vanessa
Medina Gómez, Gema
Lopez-Pedrera, Chary
Tinahones, Francisco J.
Symons, J. David
Summers, Scott A.
Ore ic, Matej
Vidal-Puig, Antonio
Keywords: Farmacologia
Farmacocinètica
Fisiologia
Metabolisme
Obesitat
Estrès oxidatiu
Pharmacology
Pharmacokinetics
Physiology
Metabolism
Obesity
Oxidative stress
Issue Date: 6-Apr-2015
Publisher: American Diabetes Association
Abstract: Adipose tissue dysfunction is an important determinant of obesity-associated, lipid-induced metabolic complications. Ceramides are well-known mediators of lipidinduced 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
Note: Reproducció del document publicat a: https://doi.org/10.2337/db14-0359
It is part of: Diabetes, 2015, vol. 64, num. 4, p. 1180-1192
URI: http://hdl.handle.net/2445/166517
Related resource: https://doi.org/10.2337/db14-0359
ISSN: 0012-1797
Appears in Collections:Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)

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