SFRP1 and obesity due to melanocortin 4 receptor deficiency: Thus, it is hypothesized that fat accumulation and obesity increase expression of sFRP-1, which blocks the Wnt-β-catenin signaling pathway, thereby enhancing adipocyte differentiation through elevation of C/EBPα and PPAR-γ while suppressing osteoblast formation via downregulation of Runx2 (Figure 1).