Although this suggests that an increase in fatty acid oxidation in these tissues, UCP3 has been identified as an important regulator of adaptive thermogenesis (increased heat production) in both skeletal muscle and BAT.37 Thus, this could be part of the mechanism providing protection from HFD-induced obesity and future studies will need to investigate if heat production is altered in Casp2−/− mice. Here, UCP3 is linked to obesity due to melanocortin 4 receptor deficiency.