CYP3A4 and obesity due to melanocortin 4 receptor deficiency: However, as obesity is a major driver of the MetS and both CYP3A4 activity and circulating 4βHC are known to be repressed by obesity and MetS [69,70], the repression of hepatic CYP3A4–circulating 4βHC–peripheral LXR pathway could link obesity and disrupted HDL-C metabolism in the obese patients with MetS.