Sphingolipid-mediated signaling pathways are described as important players in the normal functioning of neurons and non-neuronal cells of the central nervous system (CNS). Recent evidence suggests that de novo ceramide synthesis in the CNS is involved in the regulation of key physiological processes, including food intake and thermogenesis. The corollary is that conditions leading to dysfunction of ceramide metabolism in these central regions can have major consequences on the physiological regulation of energy balance. Indeed, excessive hypothalamic ceramide synthesis has been shown to lead to central insulin resistance, dysregulation of glucose homeostasis associated with changes in autonomic nervous system activity. As such, dysregulation of hypothalamic ceramide synthesis therefore constitutes a key starting point for the setting in of pathophysiological conditions such as obesity and type 2 diabetes.
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