Molecular Mechanisms Regulating BDNF and Obesity

描述(申请人提供)：肥胖和吞噬亢进是出生后大脑中缺乏脑源性神经营养因子(BDNF)的条件突变的表型。进一步的研究还发现，BDNF基因与人类肥胖和厌食症有关。由于肥胖是一种受许多不同基因调控的性状，这些基因的等位基因分离不断地导致表型的严重程度，我们建议通过关注与BDNF相互作用的基因来研究基因交互作用对肥胖的调节作用。应该注意的是，这种肥胖模型是新颖的，因为它只根据基因类型产生肥胖表型，而不受环境影响的需要。我们认为BDNF可能与下丘脑-垂体甲状腺(HPT)轴相互作用，调节下丘脑的能量调节和食物摄取。我们计划利用[微阵列]神经元细胞培养和体内操作来验证BDNF与HPT轴的相互作用，同时识别可能共同作用或不依赖BDNF表达的[新]基因，以诱导我们的数量性状动物模型中观察到的肥胖表型。

DESCRIPTION (provided by applicant): Obesity and hyperphagia are phenotypes of conditional mutants lacking Brain-Derived Neurotrophic Factor (BDNF) in the brain after birth. Further investigation has also implicated the BDNF gene in both human obesity and anorexia. Since obesity is a trait regulated by many different genes, with allelic segregation of these genes giving rise to the severity of the phenotype in a continuous manner, we propose to investigate genetic interactions regulating obesity by focusing on genes that interact with BDNF. It should be noted, that this model of obesity is novel because it gives rise to an obese phenotype based on genotype alone, independent of the need for environmental influences. We are proposing that BDNF may interact with the hypothalamic-pituitary thyroid (HPT) axis to modulate hypothalamic energy regulation and food intake. We plan to utilize [microarrays] neuronal cell culture and in vivo manipulations to verify the interactions of BDNF with the HPT axis, while simultaneously identifying [novel] genes that may interact together or independently of BDNF expression to induce the obese phenotype observed in our quantitative trait animal model.