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.