Molecular Mechanisms Regulating BDNF and Obesity

描述（由申请人提供）：肥胖和贪食是出生后大脑中缺乏脑源性神经营养因子（BDNF）的条件突变体的表型。进一步的研究也表明BDNF基因与人类肥胖和厌食症有关。由于肥胖是一种由许多不同基因调控的性状，这些基因的等位基因分离以连续的方式引起表型的严重性，我们建议通过关注与BDNF相互作用的基因来研究调节肥胖的遗传相互作用。值得注意的是，这种肥胖模型是新颖的，因为它产生的肥胖表型仅基于基因型，独立于环境影响的需要。我们提出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入。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，同时鉴定可能与BDNF表达相互作用或独立相互作用的[新]基因，以诱导我们在定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.