Browning of white adipose tissue (that is, genetic or pharmacological increase in UCP function), is protective against the development of obesity-related T2DM.26, 27 Moreover, we found an increase in expression of the transcriptional co-activator PGC-1 in the adipose tissue of caspase-2-deficient mice on Western diet, as compared with WT mice, suggesting an increase in mitochondrial biogenesis (Supplementary Figure 3). Here, UCP1 is linked to obesity due to melanocortin 4 receptor deficiency.