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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 López 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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