CYP2R1 and obesity due to melanocortin 4 receptor deficiency: Animal models demonstrated downregulation of CYP2R1 in obesity and diabetes.29 It was also shown that surgically induced weight loss in humans led to increased CYP2R1 activity in adipose tissue.29 Indeed, the effects of supplementation with vitamin D3, 2000 IU/d, on serum 25-OHD, FVD, and BioD levels were markedly attenuated across higher BMI categories.