Fuel utilization by hypothalamic neurons: roles for ROS

The hypothalamus plays a major part in regulating energy homeostasis by integrating hormonal and nutritional signals. Increasing evidence shows that specific neurons in the hypothalamus respond to changing glucose, lipid and amino acid levels. However, the intracellular substrate for such ‘fuel sensing’ and its integration into the neuronal doctrine as it relates to energy homeostasis remains elusive. Evidence points to differential fuel utilization in response to nutrient availability and free radical formation as crucial components in regulating neuronal functions. This review places these components in the context of neurobiological aspects of circuit-specific hypothalamic output, focusing on the melanocortin system. The effects of glucose and fatty acids are discussed with emphasis on free radical production in orexigenic and anorexigenic neurons of the arcuate nucleus.