Interestingly, FoxO1DAT KO mice displayed higher sucrose preference and elevated tissue dopamine content in the midbrain which is known to modulate the reward value for nutrients4142. In this regard, the minor trend towards an increase in accumulated HFD intake in KO mice (Fig. 5a) could be attributed to either higher reward value of palatable food or compensatory feedback regulation of homoeostasis from markedly increased energy expenditure in KO mice or both. Nonetheless, the difference in reward feeding is unlikely to explain the observed metabolic phenotypes of FoxO1DAT KO mice as the total food intake both in chow diet and HFD was comparable. In support of this concept, the expression of hypothalamic neuropeptides involved in feeding behaviour including Agrp, Npy, Pomc and Cart was also not changed in FoxO1DAT KO mice.
