Remarkably, the FoxO1DAT KO mice showed markedly increased energy expenditure which did not result from increased physical activity but was due to increased adaptive thermogenesis. Enhanced iBAT thermogenesis in the FoxO1DAT KO mice might be attributed to the activation of sympathetic nervous system activity as the level of norepinephrine was elevated in FoxO1DAT KO mice. In addition, increased dopamine content might also contribute to higher iBAT thermogenesis in FoxO1DAT KO mice since pharmacological studies using dopamine reuptake inhibitors have been shown to activate iBAT thermogenesis2627. Increased adaptive thermogenesis due to enhanced sympathetic activity from CNS was supported by the findings that expression of Adrb3 and downstream signalling of CA/Adrb3 including p-Creb, p-p38 MAPK, Ucp1 was markedly increased in iBAT of FoxO1DAT KO mice.
