RT Journal Article
SR Electronic
T1 A VASP-Rac–Soluble Guanylyl Cyclase Pathway Controls cGMP Production in Adipocytes
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP ra62
OP ra62
DO 10.1126/scisignal.2002867
VO 5
IS 239
A1 Jennissen, Katja
A1 Siegel, Franziska
A1 Liebig-Gonglach, Michaela
A1 Hermann, Michaela-Rosemarie
A1 Kipschull, Stefanie
A1 van Dooren, Sander
A1 Kunz, Wolfram S.
A1 Fässler, Reinhard
A1 Pfeifer, Alexander
YR 2012
UL http://stke.sciencemag.org/content/5/239/ra62.abstract
AB The ubiquitous second messenger cyclic guanosine monophosphate (cGMP) plays an important role in metabolism and promotes brown adipocyte differentiation. We showed that ablation of the gene encoding vasodilator-stimulated phosphoprotein (VASP), a major downstream component of the cGMP signaling cascade, increased cellular cGMP content in brown and white adipocytes and mouse embryonic fibroblasts. VASP-deficient cells showed increased activation of Rac1, which in turn increased the abundance of the cGMP-producing enzyme soluble guanylyl cyclase (sGC), the main receptor for nitric oxide. Consequently, loss of VASP caused increased cGMP concentrations and enhanced brown adipocyte differentiation. Consistent with the in vitro data, we found increased energy expenditure in VASP-deficient mice and exposure to cold triggered enhanced lipolysis and cellular respiration in VASP-deficient brown fat cells. In addition, VASP-deficient mice exhibited increased development of brown-like adipocytes in white fat. Our data revealed that a VASP to Rac to sGC negative feedback loop limited cGMP production, thereby regulating adipogenesis and energy homeostasis.