PRDM16 and obesity due to melanocortin 4 receptor deficiency: For example, inhibition of the key transcriptional factor PRDM16 or reduction of UCP1 which is both involved in the UCP1-dependent pathway can drive obesity.57,58 Similarly, in the process of UCP1-independent thermogenesis, suppression of any one of the three futile metabolic cycling mechanisms can cause obesity.