Molecular Mechanisms Regulating BDNF and Obesity

调节 BDNF 和肥胖的分子机制

• 批准号: 7256282
• 负责人: MARDI Susanna BYERLY
• 金额: $ 1.62万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7256282
• 关键词: Adipose tissue; Adult; Age; Alleles; Animal Model; Animals; Anorexia; Area; Birth; Body Composition; Body Weight; Brain; Brain-Derived Neurotrophic Factor; Breeding; Cell Nucleus; Chickens; Child; Cultured Cells; Developed Countries; Developing Countries; Development; Diet; Dissociation; Eating; Eating Disorders; Endocrine; Energy Metabolism; Epidemic; Etiology; Exhibits; Fatty acid glycerol esters; Feedback; Food Intake Regulation; Gene Expression; Generations; Genes; Genetic; Genotype; Health; Health Care Costs; Human; Hyperphagia; Hyperthyroidism; Hypothalamic structure; Hypothyroidism; In Vitro; Investigation; Lateral; Lesion; Maps; Mediator of activation protein; Messenger RNA; Metabolic; Metabolism; Modeling; Molecular; Neurons; Numbers; Obesity; Overweight; Phenotype; Physiological; Pituitary Gland; Process; Proteins; Quality of life; Rate; Rattus; Receptor Protein-Tyrosine Kinases; Regulation; Relative (related person); Serum; Severities; Signal Transduction; Thinness; Thyroid Gland; Thyrotropin-Releasing Hormone; Tissue-Specific Gene Expression; Triiodothyronine; Week; World Health Organization; Zucker Rats; base; feeding; improved; in vivo; interest; mutant; novel; paraventricular nucleus; pituitary thyroid axis; response; segregation; stem; trait

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.

描述（由申请人提供）：肥胖和摄食过多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。进一步的研究还表明，BDNF基因与人类肥胖和厌食症有关。由于肥胖是由许多不同的基因调控的性状，这些基因的等位基因分离引起的表型的严重程度在一个连续的方式，我们建议调查遗传相互作用调节肥胖的基因，重点是与BDNF相互作用的基因。应该注意的是，这种肥胖模型是新颖的，因为它产生了肥胖表型，仅基于基因型，不需要环境影响。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表达一起或独立地相互作用以诱导在我们的数量性状动物模型中观察到的肥胖表型的[新]基因。