Fig. 8: Reactivation of ADCY3 signaling enhances the motility of ASCs from donors with obesity.

Analysis of cell motility. A Experimental schedule of treatment with the ADCY inhibitor SQ22536 (SQ) or its activator NKH477 (NKH). B Representative trajectories are depicted for individual cells (n = 1, 50 cells in each group). The velocity (C), the accumulated distance (D), and the directionality (E) of ASC motility are shown as mean ± SD (n = 3, 150 cells pooled from three experiments). Statistical significance was analyzed with the Kruskal-Wallis test followed by Dunn’s multiple comparison test. *p < 0.05; ***p < 0.001; n.s., not significant. F Schematic illustration of the proposed working model. Obesity-associated factors, such as TGFβ, are able to shortened primary cilia in ASCs associated with deregulated pathways and genes/proteins, fueling inflammation and metabolic dysfunction and facilitating the progression of obesity. Treatment with NHK477 reactivates the ADCY3-cAMP signaling axis, prolongs the primary cilium, improves cell motility, and thus possibly prevents the progression of obesity. Abbreviations: ADCY3 adenylate cyclase 3, ADIPOQ adiponectin, cAMP cyclic adenosine monophosphate, CDH1 cadherin-1, COL collagen, CXCL12 CXC motif chemokine 12, DMSO dimethyl sulfoxide, FABP4 fatty acid-binding protein 4, FN1 fibronectin, HH hedgehog, ITGB5 integrin beta 5, ln lean, LPL lipoprotein lipase, ob obese, PGF placental growth factor, PPARG peroxisome proliferator-activated receptor gamma, TGFβ transforming growth factor-β, THBS1 thrombospondin 1.