Trk B signaling in dopamine 1 receptor neurons regulates food intake and body weight

OBJECTIVE: Loss of BDNF-TrkB signaling results in obesity in both humans and mice; however, the neural circuit that mediates this effect is unknown. We tested the role of TrkB signaling dopamine-1 receptor expressing neurons in body weight regulation. DESIGN AND METHODS: Mice with a floxed allele of the TrkB gene were paired with mice expressing Cre-recombinase under control of the D1 promoter in order to conditionally knock out expression of TrkB receptors from D1-neurons. RESULTS: Deletion of TrkB receptors from D1 neurons results in obesity in chow fed mice due to increased feed efficiency. In contrast, loss of Trk B signaling in D1 neurons induced hyperphagia and hyperglycemia in mice maintained on high fat diet. CONCLUSIONS: These findings indicate TrkB signaling in D1 neurons regulates body weight by distinct mechanisms for chow and high fat diet and may be important for defending the body against the development of obesity and obesity-related disorders.