Central role of soluble guanylyl cyclase/cGMP signaling in adipocytes

Two types of fat can be distinguished: White adipose tissue (WAT) is the primary site for energy storage whereas brown adipose tissue (BAT) consumes energy to generate heat. Obesity is the pathological increase of WAT which negatively affects health. Stimulation of BAT to dissipate energy might be used to balance metabolism and fight life threatening obesity related diseases such as stroke and type 2 diabetes.

The role of soluble guanylyl cyclase (sGC)/cGMP signaling pathway was investigated in adipocytes in vitro. The stromal vascular fraction was isolated from BAT of sGC-/- mice and their wildtype (wt) littermates and was differentiated in vitro into adipocytes in the presence or absence of 8-pCPT-cGMP.

RedO staining of accumulated intracellular lipids was reduced in sGC-/- cells compared to wt cells and, accordingly, sGC-/- cells contained approximately 50% less intracellular triglycerides than wt cells. Expression levels of adipogenic marker proteins PPARg, C/EBPb, aP2 were also reduced in sGC-/- cells compared to wt cells.

Thermogenic marker genes UCP1, PGC1a, and Cidea were expressed at lower levels in sGC-/- than in wt cells. Also, thermogenic function as assessed by lipolytic capacity in brown adipocytes was impaired in sGC deficient cells.

Importantly, addition of cGMP throughout differentiation restored adipogenic differentiation in sGC-/- cells.

Together these results show that sGC is an important source of cGMP during adipogenic and thermogenic differentiation. The pivotal role of sGC/cGMP signaling in adipose tissue might be used in pharmacological therapy to treat obesity and related disorders in the future.