Editors' ChoiceMedicine

Nurturing the Impulse to Supersize

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Science Translational Medicine  03 Mar 2010:
Vol. 2, Issue 21, pp. 21ec34
DOI: 10.1126/scitranslmed.3000999

Recent years have witnessed an explosion in obesity and obesity-related illness, with particularly ominous numbers among children and adolescents. In response, translational investigators have asked what characteristics within the brain determine whether an individual has an eating pattern that puts him at high risk for obesity, such as a preference for foods with high fat content. A new study shows that brain-derived neurotrophic factor (BDNF)—the brain’s main growth factor—within the brain’s reward system is altered in rodents by consumption of high-fat foods. The neural reward center encompasses the mesolimbic neurons that connect the midbrain to the nucleus accumbens and uses dopamine as a neurotransmitter. Cordeira and colleagues found that mice that were fed a high-fat meal showed changes in mRNA expression for BDNF (decreased) and its receptor (TrkB) (increased) in the ventral tegmental area, where mesolimbic dopamine neurons arise. In addition, mice depleted of BDNF, either throughout the brain or just in the ventral tegmentum, ate more calories than did wild-type mice, despite getting the same amounts of exercise. These mice also showed decreased dopamine release in a key reward-processing region within the nucleus accumbens, and in the dorsal striatum, which mediates automatic, highly learned behaviors. Decreased dopamine was accompanied by decreased numbers of striatal D2 receptors, as is also seen in obese animals and humans. Of most interest is the fact that administration of a selective D1 receptor agonist to these mice completely normalized their high-fat food intake. These results suggest that BDNF in the mesolimbic dopamine system regulates the hedonic processes associated with eating. Disrupted BDNF regulation could lead to a reward-deficient state which in turn could cause compensatory overeating, especially of calorie-dense foods, in an effort to increase reward. This work offers both a refined model of cerebral pathophysiology of obesity and eating disorders, as well as potential treatment targets for these conditions.

J. W. Cordeira et al., Brain-derived neurotrophic factor regulates hedonic feeding by acting on the mesolimbic dopamine system. J. Neurosci. 30, 2533–2541 (2010). [Abstract]

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