Genetics of obesity and energy metabolism

该项目的主要目的是确定人类肥胖的遗传和/或分子原因。我们正在对肥胖靶基因进行测序，以发现可能与20例青春期前Pima印第安病例（选择为严重肥胖的早期发病）和20例性别和年龄匹配的瘦对照组中肥胖相关的多态性。在过去的一年里，我们研究了黑皮质素受体-4，并没有发现感兴趣的多态性。序列分析 神经肽Y受体-5证实了先前发现的与成年Pimas肥胖相关的几种多态性。我们也在研究肥胖和消瘦的成年捐赠者死后大脑样本中的差异基因表达，使用人类神经生物学微阵列。在过去一年，我们完成了一项研究，以测试该方法的可靠性，这似乎是可以接受的。为了揭示潜在的暴食/肥胖症的可能的常见神经化学缺陷，我们计划开始研究下丘脑（控制动物和人类饮食行为的许多方面）中的差异基因表达。我们已经在1个肥胖和1个瘦供体中完成了这样的实验。

The main aims of this projects are to identify the genetic and/or molecular cause(s) of obesity in humans. We are sequencing obesity target genes to find polymorphisms that may be associated with obesity in a group of 20 prepubertal Pima Indian cases (selected for early onset of severe obesity) and 20 sex- and age-matched lean controls. In the past year we have studied the melanocortin receptor-4 and found no polymorphisms of interest. Sequencing of the the neuropeptide Y receptor-5, has confirmed several polymorphisms previously found to be associated with obesity in adult Pimas. We are also studying differential gene expression in post-mortem brain samples from obese and lean adult donors, using a human neurobiology microarray. In the past year we have completed a study to test the reliability of the methodology, which appears to be acceptable. To uncover possible common neurochemical defects underlying hyperphagia/obesity, we plan to begin by studying differential gene expression in the hypothalamus (which controls many aspects of eating behavior in animals and humans). We have completed one such experiment in 1 obese and 1 lean donor.