Mason Brittany L, Lobo Mary Kay, Parada Luis F, Lutter Michael
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Obesity (Silver Spring). 2013 Nov;21(11):2372-6. doi: 10.1002/oby.20382. Epub 2013 May 31.
Loss of BDNF-TrkB signaling results in obesity in both humans and mice; however, the neural circuit that mediates this effect is unknown. The role of TrkB signaling in dopamine-1 receptor expressing neurons in body weight regulation was tested.
Mice with a floxed allele of the TrkB gene were paired with mice expressing Cre-recombinase under control of the D1 promoter to conditionally knock out expression of TrkB receptors from D1-neurons.
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.
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.
脑源性神经营养因子（BDNF）-酪氨酸激酶受体B（TrkB）信号通路的缺失会导致人类和小鼠肥胖；然而，介导这种效应的神经回路尚不清楚。本研究测试了TrkB信号在表达多巴胺-1受体的神经元中对体重调节的作用。
将携带TrkB基因floxed等位基因的小鼠与在D1启动子控制下表达Cre重组酶的小鼠配对，以有条件地敲除D1神经元中TrkB受体的表达。
由于饲料效率提高，从D1神经元中删除TrkB受体会导致喂食普通饲料的小鼠肥胖。相比之下，在高脂饮食喂养的小鼠中，D1神经元中TrkB信号的缺失会导致食欲亢进和高血糖。
这些发现表明，D1神经元中的TrkB信号通过不同的机制调节普通饲料和高脂饮食的体重，可能对保护机体免受肥胖及肥胖相关疾病的发生具有重要意义。
