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Central dopaminergic circuitry controlling food intake and reward: implications for the regulation of obesity

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Prevalence of obesity in the general population has increased in the past 15 years from 15% to 35%. With increasing obesity, the coincident medical and social consequences are becoming more alarming. Control over food intake is crucial for the maintenance of body weight and represents an important target for the treatment of obesity. Central nervous system mechanisms responsible for control of food intake have evolved to sense the nutrient and energy levels in the organism and to coordinate appropriate responses to adjust energy intake and expenditure. This homeostatic system is crucial for maintenance of stable body weight over long periods of time of uneven energy availability. However, not only the caloric and nutritional value of food but also hedonic and emotional aspects of feeding affect food intake. In modern society, the increased availability of highly palatable and rewarding (fat, sweet) food can significantly affect homeostatic balance, resulting in dysregulated food intake. This review will focus on the role of hypothalamic and mesolimbic/mesocortical dopaminergic (DA) circuitry in coding homeostatic and hedonic signals for the regulation of food intake and maintenance of caloric balance. The interaction of dopamine with peripheral and central indices of nutritional status (e.g., leptin, ghrelin, neuropeptide Y), and the susceptibility of the dopamine system to prenatal insults will be discussed. Additionally, the importance of alterations in dopamine signaling that occur coincidently with obesity will be addressed. Copyright © 2010 John Wiley & Sons, Inc.

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Figure 1.

Dopamine interactions in the CNS. Dopamine cells in the VTA express receptors for numerous molecules important in the central regulation of food intake. Dopamine neurons project widely to numerous areas that express D1 and D2 dopamine receptors. There are extensive interactions between these regions. *Note: Receptor colocalization has not been experimentally examined for each receptor subtype.

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Blanche Capel

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earned her Ph.D. at the University of Pennsylvania and has been at Duke University since 1993. She earned her endowed professorship, the James B. Duke Professor of Cell Biology, for the meaningful discoveries she has made since her postdoctoral work in genetics at the National Institute for Medical Research in London. The broad goal of the research in Dr. Capel’s laboratory is to characterize the cellular and molecular basis of morphogenesis – how the body forms. She uses gonadal (gender/sex) development in the mouse as her model system and investigates a gene she helped discover, Sry, the male sex determining gene. Gonad development is unique in that a single rudimentary tissue can be induced to form one of two different organs, an ovary or testis, and she is learning all she can about this central mystery of biology.

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