Although the metabolic function of FoxO1 has been well-established in specific subsets of neurons in the hypothalamus, particularly in the AgRP and POMC neurons of the ARC5, recent studies have suggested that the function of FoxO1 in the CNS might extend beyond the hypothalamus. Heinrich et al8. reported that deletion of FoxO1 in majority of hypothalamic neurons using transgenic mice expressing Nkx2.1-cre resulted in normal food intake and energy expenditure and did not protect the mice from diet-induced obesity suggesting the heterogeneity of FoxO1 function within the hypothalamus. However, using synapsin-Cre to ablate FoxO1 in broad neuronal populations with minimal effect on AgRP and POMC neurons, Ren et al6. found that Syn-FoxO1 KO mice exhibited a catabolic energy metabolism phenotype associated with increased locomotor activity and blunted re-feeding response due to enhanced sensitivity to hormonal and nutritional signalling pathway in the CNS. Moreover, Syn-FoxO1 KO mice showed increased energy expenditure and resistance to HFD-induced obesity6. These combined data indicate the metabolic role of FoxO1 in other neuronal populations outside of the hypothalamus.
