Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function

Nuria Barbarroja (Corresponding Author), Sergio Rodriguez-Cuenca, Heli Nygren, Antonio Camargo, Ana Pirraco, Joana Relat, Irene Cuadrado, Vanessa Pellegrinelli, Gema Medina-Gomez, Chary Lopez-Pedrera, Francisco J. Tinahones, J. David Symons, Scott A. Summers, Matej Oresic, Antonio Vidal-Puig

Research output: Contribution to journalArticleScientificpeer-review

29 Citations (Scopus)

Abstract

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 catalysing 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 validate 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.
Original languageEnglish
Pages (from-to)1180-1192
JournalDiabetes
Volume64
Issue number4
DOIs
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

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