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Trends Endocrinol Metab. 2009 Mar;20(2):78-87. doi: 10.1016/j.tem.2008.10.003. Epub 2008 Dec 10.

Fuel utilization by hypothalamic neurons: roles for ROS.

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  • 1Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.


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.

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