The increase in dopamine contents in the midbrain led us to ask whether there is any change in dopamine receptor 2 (D2R) signalling. Interestingly, we observed modest reduction in D2R expression in the midbrain of the FoxO1 KODAT mice (Supplementary Fig. 5a and b). Although the relationship between obesity and D2R receptor availability is still controversial, altered D2R receptor availability has been implicated in over-eating and obesity development293031323334. However, we did not observe any difference in total food intake (both normal chow (NC) and HFD) in the FoxO1 KODAT mice even though those mice exhibited modestly increased sucrose preference and increasing trend in the HFD consumption during metabolic chamber analyses (Figs 4,5a). Moreover, there was no difference in physical activity (Fig. 5b and Supplementary Fig. 4a). It is likely that decreased D2R expression in the KO mice was not a primary effect of DA FoxO1 deletion, but a secondary effect due to compensatory feedback regulation from the increase in dopamine content.
