It is known that increased sympathetic flow from the CNS to iBAT plays an important role in the activation of thermogenesis2425 and the central DA activity in addition is involved in the regulation of iBAT thermogenesis2627. Therefore, we wondered whether FoxO1 ablation in DA neurons would have any effects on iBAT thermogenesis. Indeed, the genes regulating iBAT thermogenesis including Adrb3, Pgc1α, Ucp1 and Ucp3 were significantly increased in KO mice (Fig. 6c). Consistent with increased level of CAs, iBAT of KO mice showed significantly increased levels of Ucp1 and phosphorylation of Creb and p38 MAPK which are downstream targets of CA/Adrb3 signalling28 (Fig. 6d,e and Supplementary Fig. 7). In addition, iBATs of KO mice showed increased UCP1 staining, mitochondrial DNA contents and less lipid accumulation (Fig. 6f,g). These data suggest that increased sympathetic activity might contribute to the increased energy expenditure and resistance to diet-induced obesity phenotype in FoxO1 KODAT mice.
