In order to maintain energy and glucose homeostasis, the brain must be able to sense and integrate metabolic feedback information from both nutrient and hormonal signals. The hypothalamus is a key region involved in sensing and integrating this metabolic information into behavioural and physiological outputs that maintain homeostasis. Within the hypothalamic two key neuronal populations have emerged as fundamentally important; Proopiomelanocortin (POMC) and Agouti-related peptide (AgRP) neurons. Genetic ablation of POMC neurons in adulthood causes severe obesity and glucose intolerance in mice and mutations in the POMC neural pathway is the most common cause of inheritable obesity in humans. On the other hand, genetic ablation of AgRP neurons causes starvation and weight loss. Thus, POMC and AgRP neurons reciprocally regulate positive and negative energy balance respectively. Although we understand the importance of these neurons in the maintenance of energy and glucose homeostasis, we know very little about how these neurons sense changes in metabolic state or how they integrate both nutrient and hormonal cues to maintain homeostasis. In order to address these questions we have focussed on mitochondrial metabolism since the metabolic processing of nutrients is required for sensing to occur. In particular, we focus on carnitine metabolism because it is juxtaposed fat and glucose metabolism making it an ideal candidate to simultaneously integrate these nutrients. Moreover, genes involved in carnitine metabolism are known to regulate hormonal sensitivity of hypothalamic neurons. We have specifically deleted genes involved in carnitine metabolism from both AgRP and POMC neurons and observed significant impacts on energy and glucose homeostasis. Carnitine acetyltransferase (Crat) in AgRP neurons regulates liver function in order to appropriately control glucose production whereas Crat in POMC neurons restricts accumulation of adipose tissue on a HFD. Collectively, our studies show that Crat is required in AgRP and POMC neurons in order to maintain energy and glucose homeostasis.