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Overeating and obesity triggered by lack of BDNF
Date:12/27/2007

from overconsumption of calories. Normal body weight was restored in mutant mice when food access was limited to that of normal mice, indicating that deletion of the Bdnf gene in the VMH and DMH does not affect the expenditure side of the energy balance equation, adds Rios.

In a series of related experiments, the researchers used advanced molecular and surgical techniques to measure levels of BDNF mRNA, a precursor of active BDNF protein, in relation to nutritional status. Thaddeus Unger, a graduate student at the Sackler School and the studys first author, describes the results of these analyses. The amount of BDNF mRNA produced decreased during periods of fasting. However, when the mice were exposed to glucose, a macronutrient, Unger notes, we observed a rapid, but transient, increase in the expression of BDNF and its receptor. These changes occurred specifically in the VMH, which is known to be involved in the regulation of food intake. The researchers confirmed that glucose acts directly in the brain, rather than through peripheral pathways, to increase BDNF expression. Direct administration of BDNF into the brain, states Rios, also led to an immediate increase in the levels of an early-response gene and marker of nerve-cell activation in both the VMH and the DMH. These results suggest that BDNF is a fast-acting signal inducing neuronal activity within neural circuits involved in appetite control.

Mice with site-specific perturbation of BDNF expression did not exhibit behavioral abnormalities typically observed in mice with global deletion of the Bdnf gene throughout the brain, such as hyperaggression, depressive-like behavior, and hyperactivity, notes Rios. The absence of these behaviors suggests that BDNF expression in the VMH and DMH is not required for regulation of non-appetite-related behaviors.

Our results establish that BDNF plays a prominent and direct role in the regulation of energy balance in adult mice. states Rios. It ap
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Contact: Siobhan Gallagher
siobhan.gallagher@tufts.edu
617-636-6586
Tufts University, Health Sciences
Source:Eurekalert

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