The neural mechanisms controlling food intake and body weight have traditionally been ascribed to neuroendocrine and nutrient feedback. Within this homeostatic framework, hunger-sensing agouti-related peptide (AgRP) neurons increase food intake and bodyweight in response to feedback signals of energy deprivation. However, recent studies show that AgRP neurons receive significant sensory input from other brain regions, which regulates food intake. This sensory input provides important learned external information about food availability and palatability, which is integrated with mood and stress levels, to affect current and future motivated food-seeking and foraging. Although these neural circuits transmitting sensory information to hypothalamic feeding centres remain unknown, they may have important roles to override the homeostatic control of feeding behaviour and drive excessive consumption in the absence of hunger or suppress feeding in the presence of hunger. Indeed, overriding this homeostatic control of feeding may underlie different pathological states characterised by abnormal feeding behaviour such as obesity or anorexia nervosa. Recently a novel stress-sensitive neural pathway from the medial prefrontal cortex (mPFC) to lateral hypothalamus (LH) was identified to suppress feeding behaviour. Hence, we hypothesised an interaction between the mPFC-LH pathway and AgRP neurons that may affect food intake, feeding behaviour, and body weight. We show that chemogenetic activation of the mPFC-LH pathway supressed baseline and ghrelin-induced AgRP activity assessed using in vivo calcium imaging. Furthermore, via optogenetics and viral techniques, we also demonstrate its effect on bodyweight, food intake, and metabolism. These studies establish a top-down, novel cortico-hypothalamic network controlling food intake and metabolism.