The WNT inhibitor Dickkopf 1 and bone morphogenetic protein 4 rescue adipogenesis in hypertrophic obesity in humans

Overweight characterized by inappropriate expansion of adipose cells (hypertrophic obesity) is associated with the metabolic syndrome and is caused by an inability to recruit and differentiate new precursor cells. We examined the role of bone morphoge-netic protein 4 (BMP4) and WNT activation in the regulation of human adipose cell differentiation. Cluster of differentiation (CD) 14+/45+ and CD31+ cells were first removed before the remaining stromal vascular cells of human subcutaneous biopsy specimens were differentiated with/without different WNT inhibitors and/or BMP4. Inhibition of WNT and induction of Dickkopf 1 (DKK1) were markers of precursor cells undergoing excellent differenti-ation. The addition of DKK1 inhibited WNT activation and pro-moted adipogenesis in cells with a low degree of differentiation. The positive effect of DKK1, inhibiting cellular WNT activation by binding to the Kremen/LDL receptor–related protein receptors