Figure 1.

CCK1R dysfunction in the obesity continuum. Shown is the CCK1R dysfunction in the clinical continuum that initially starts with susceptibility to gain weight, and eventually leads to obesity and metabolic syndrome. In the earlier stages, CCK1R exhibits normal binding and stimulus–activity coupling, whereas during the later stages there is a significant increase in membrane cholesterol, which results in an increased binding affinity, but reduced G protein coupling efficiency, with 22.5-fold more receptors required to achieve the same half-maximal response. Dotted lines indicate the IC₅₀ and EC₅₀ values at normal and high levels of membrane cholesterol, respectively.