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Central nervous system control of food intake

Abstract

New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of key signalling molecules involved in this regulatory system highlights its importance to human health. Although each new signalling pathway discovered in the hypothalamus is a potential target for drug development in the treatment of obesity, the growing number of such signalling molecules indicates that food intake is controlled by a highly complex process. To better understand how energy homeostasis can be achieved, we describe a model that delineates the roles of individual hormonal and neuropeptide signalling pathways in the control of food intake and the means by which obesity can arise from inherited or acquired defects in their function.

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Figure 1: Model showing how a change in body adiposity is coupled to compensatory changes of food intake.
Figure 2: Role of arcuate nucleus neurons in adiposity signalling.
Figure 3: Diagrams of rat brain, showing major hypothalamic regions implicated in adiposity signalling and regulation of food intake.
Figure 4: NPY/AGRP and POMC/CART neurons in the arcuate nucleus, adjacent to the third ventricle, are first-order neurons in the hypothalamic response to the circulating adiposity signals insulin and leptin.
Figure 5: Locations of candidate second-order neurons involved in the hypothalamic response to insulin and leptin adiposity signalling.
Figure 6: Neuroanatomical model of pathways by which adiposity signals, leptin (secreted by adipocytes) and insulin (secreted by the endocrine pancreas in proportion to adiposity), interact with central autonomic circuits regulating meal size.

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Acknowledgements

Assistance in manuscript preparation provided by L. Walters and in figure preparation by M. Baskin is gratefully acknowledged. This work was supported by NIH grants, the Diabetes Endocrinology Research Center and Clinical Nutrition Research Unit of the University of Washington, and the Department of Veterans Affairs.

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Schwartz, M., Woods, S., Porte, D. et al. Central nervous system control of food intake. Nature 404, 661–671 (2000). https://doi.org/10.1038/35007534

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