Ogino Tomoe, Moralejo Daniel H, Kose Hiroyuki, Yamada Takahisa, Matsumoto Kozo
Institute for Animal Experimentation, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770-8503, Japan.
Mamm Genome. 2003 Dec;14(12):839-44. doi: 10.1007/s00335-003-2295-7.
Leptin is produced by adipose tissue and acts as a feedback signal to the hypothalamus controlling energy homeostasis, by reducing food consumption and increasing energy expenditure. Because serum leptin levels are highly correlated with body fat mass, they can be used as an index to predict obesity-related diseases. However, the identity of genetic factors that influence the obesity and the obesity-related metabolic disorders remains largely unknown. In this study, we performed a whole-genome scan search, using 382 F2 intercross progeny between the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model for obese type 2 diabetes in human, and F344 rat, in order to identify loci responsible for the regulation of leptin and other obesity-related plasma substances. We have identified two quantitative trait loci (QTLs) contributing to serum leptin levels. These two loci, designated Olep1 [Chromosome (Chr) 2] and Olep2 (Chr 6), were homologous to those of human genome regions containing several potential candidate genes for obesity. These are fatty acid-binding protein 2 (FABP2), FABP4, and FABP5 for Olep1, and proopiomelanocortin (POMC) and glucose regulatory protein (GCKR) for Olep2.
瘦素由脂肪组织产生，通过减少食物摄入和增加能量消耗，作为一种反馈信号作用于下丘脑，控制能量平衡。由于血清瘦素水平与体脂量高度相关，它们可作为预测肥胖相关疾病的一个指标。然而，影响肥胖及肥胖相关代谢紊乱的遗传因素仍大多未知。在本研究中，我们利用大冢长-埃文斯-德岛肥胖（OLETF）大鼠（一种人类肥胖型2型糖尿病动物模型）与F344大鼠之间的382个F2代杂交后代进行全基因组扫描搜索，以确定负责调控瘦素及其他肥胖相关血浆物质的基因座。我们已鉴定出两个影响血清瘦素水平的数量性状基因座（QTL）。这两个基因座，分别命名为Olep1[染色体（Chr）2]和Olep2（Chr 6），与人类基因组区域中包含几个肥胖潜在候选基因的区域同源。对于Olep1，这些基因是脂肪酸结合蛋白2（FABP2）、FABP4和FABP5；对于Olep2，则是阿黑皮素原（POMC）和葡萄糖调节蛋白（GCKR）。
