Weigle D S, Kuijper J L
Department of Medicine, University of Washington School of Medicine, Seattle, USA.
Bioessays. 1996 Nov;18(11):867-74. doi: 10.1002/bies.950181105.
Physiological investigation has demonstrated that the central nervous system monitors body composition and adjusts energy intake and expenditure to stabilize total adipose tissue mass. Genetic variations in the signalling molecules involved in this regulatory system account for the heritable component of body fat content. The application of molecular techniques to rodent models of Mendelian obesity has resulted in the characterization of five loci at which mutations produce an abnormal accumulation of body fat. The genes at these loci include agouti, which encodes a molecule that antagonizes the binding of alpha melanocyte-stimulating hormone to its receptor; fat, which encodes carboxypeptidase E; tubby, which encodes a putative phosphodiesterase; obese, which encodes a circulating satiety protein; and diabetes, which encodes the receptor for the obese gene product. A more detailed understanding of the functional interrelationships of these genes should lead to important new insights into the causes and potential therapies for human obesity.
生理学研究表明，中枢神经系统会监测身体组成，并调整能量摄入与消耗，以稳定总脂肪组织量。参与此调节系统的信号分子的基因变异构成了体脂含量的遗传成分。将分子技术应用于孟德尔肥胖症的啮齿动物模型，已鉴定出五个位点，这些位点的突变会导致身体脂肪异常堆积。这些位点的基因包括刺鼠基因，其编码一种可拮抗α黑素细胞刺激素与其受体结合的分子；脂肪基因，其编码羧肽酶E；肥胖基因，其编码一种假定的磷酸二酯酶；肥胖蛋白基因，其编码一种循环饱腹感蛋白；以及糖尿病基因，其编码肥胖基因产物的受体。对这些基因功能相互关系的更详细了解，应能为人类肥胖症的病因及潜在治疗方法带来重要的新见解。
