Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas during 6 or 12 hours. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone bodies level detection. First, an increase in food intake appeared over a 12-hour period of brain ketone bodies perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as of phosphorylated AMPK and is due to ketone bodies sensed by the brain as blood ketone bodies levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 hours of ketone bodies perfusion which reversed to normal at 12 hours of perfusion. Altogether, these results suggest that an increase in brain ketone bodies concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.