PT  - JOURNAL ARTICLE
AU  - Jennissen, Katja
AU  - Siegel, Franziska
AU  - Liebig-Gonglach, Michaela
AU  - Hermann, Michaela-Rosemarie
AU  - Kipschull, Stefanie
AU  - van Dooren, Sander
AU  - Kunz, Wolfram S.
AU  - Fässler, Reinhard
AU  - Pfeifer, Alexander
TI  - A VASP-Rac–Soluble Guanylyl Cyclase Pathway Controls cGMP Production in Adipocytes
AID  - 10.1126/scisignal.2002867
DP  - 2012 Aug 28
TA  - Science Signaling
PG  - ra62--ra62
VI  - 5
IP  - 239
4099  - http://stke.sciencemag.org/content/5/239/ra62.short
4100  - http://stke.sciencemag.org/content/5/239/ra62.full
SO  - Sci. Signal.2012 Aug 28; 5
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.