Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA ; Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
Mol Metab. 2013 Aug 9;2(4):491-7. doi: 10.1016/j.molmet.2013.08.002. eCollection 2013.
Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB (tropomyosin receptor kinase B), are widely expressed in the brain where they regulate a wide variety of biological processes, including energy homeostasis. However, the specific population(s) of TrkB-expressing neurons through which BDNF governs energy homeostasis remain(s) to be determined. Using the Cre-loxP recombination system, we deleted the mouse TrkB gene in RGS9-2-expressing cells. In this mouse mutant, TrkB expression was abolished in several hypothalamic nuclei, including arcuate nucleus, dorsomedial hypothalamus, and lateral hypothalamus. TrkB expression was also abolished in a small number of cells in other brain regions, including the cerebral cortex and striatum. The mutant animals developed hyperphagic obesity with normal energy expenditure. Despite hyperglycemia under fed conditions, these animals exhibited normal fasting blood glucose levels and normal glucose tolerance. These results suggest that BDNF regulates energy homeostasis in part through TrkB-expressing neurons in the hypothalamus.
脑源性神经营养因子（BDNF）及其同源受体 TrkB（原肌球蛋白受体激酶 B）在大脑中广泛表达，调节着包括能量平衡在内的多种生物学过程。然而，BDNF 调节能量平衡所通过的 TrkB 表达神经元的具体亚群仍有待确定。利用 Cre-loxP 重组系统，我们在 RGS9-2 表达细胞中删除了小鼠 TrkB 基因。在这种小鼠突变体中，TrkB 表达在包括弓状核、下丘脑背内侧核和下丘脑外侧核在内的几个下丘脑核中被消除。TrkB 表达也在其他脑区的少数细胞中被消除，包括大脑皮层和纹状体。突变动物表现出多食性肥胖和正常的能量消耗。尽管在进食状态下存在高血糖，但这些动物表现出正常的空腹血糖水平和正常的葡萄糖耐量。这些结果表明，BDNF 通过下丘脑内表达 TrkB 的神经元调节能量平衡。
