Genetic factors contributing to obesity and body weight can act through mechanisms affecting muscle weight, fat weight, or both
Genetic factors contributing to obesity and body weight can act through mechanisms affecting muscle weight, fat weight, or both
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DOI：
10.1152/physiolgenomics.90277.2008
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发表时间：
2009-01-01
影响因子：
4.6
通讯作者：
Li, Renhua
中科院分区：
文献类型：
--
作者：
Brockmann, Gudrun A.;Tsaih, Shirng-Wern;Li, Renhua
Brockmann GA、Tsaih SW、Neuschl C、Churchill GA、Li R。导致肥胖和体重的遗传因素可以通过影响肌肉重量、脂肪重量或两者的机制发挥作用。 Physiol Genomics 36: 114-126, 2009。首次发表于 2008 年 11 月 4 日； doi:10.1152/physicalgenomics.90277.2008.-体重和亚表型（例如脂肪重量）的遗传位点已被反复绘制。然而，在绘图研究中通常没有考虑不同基因座的独特影响以及不同性状之间的生理相互作用。在这里，我们使用结构方程建模的方法来确定遗传位点与影响体重的不同表型之间的具体关系。使用这种技术，我们能够区分影响肥胖的基因位点和影响肌肉生长的基因位点。我们检查了高体重选择的小鼠品系 NMRI8 和 DU6i 以及杂交群体 NMRI8 x DBA/2 和 DU6i x DBA/2。结构模型帮助我们了解遗传因素是否多效性或非多效性影响瘦体重和脂肪量。性别对脂肪和肌肉重量都有直接影响，但也会通过肌肉重量间接影响脂肪重量。在这两个杂交中鉴定出的三个基因位点显示出对脂肪沉积的独特影响，五个基因座仅对肌肉重量有贡献。另外两个基因座对脂肪和肌肉重量显示出多效性作用，其中一个基因座在两个杂交中都起作用。脂肪重量和肌肉重量受到上位效应的影响。我们提供的证据表明，为体重选择的菌株中的显着脂肪位点通过对瘦体重的影响直接或间接地影响脂肪重量。这些结果为数量性状基因座区域中基因的作用提供了新的线索，这些基因座区域可能影响肌肉和脂肪量，从而将体重作为一个复合性状进行控制。
Brockmann GA, Tsaih SW, Neuschl C, Churchill GA, Li R. Genetic factors contributing to obesity and body weight can act through mechanisms affecting muscle weight, fat weight, or both. Physiol Genomics 36: 114-126, 2009. First published November 4, 2008; doi:10.1152/physiolgenomics.90277.2008.-Genetic loci for body weight and subphenotypes such as fat weight have been mapped repeatedly. However, the distinct effects of different loci and physiological interactions among different traits are often not accounted for in mapping studies. Here we used the method of structural equation modeling to identify the specific relationships between genetic loci and different phenotypes influencing body weight. Using this technique, we were able to distinguish genetic loci that affect adiposity from those that affect muscle growth. We examined the high body weight-selected mouse lines NMRI8 and DU6i and the intercross populations NMRI8 x DBA/2 and DU6i x DBA/2. Structural models help us understand whether genetic factors affect lean mass and fat mass pleiotropically or nonpleiotropically. Sex has direct effects on both fat and muscle weight but also influences fat weight indirectly via muscle weight. Three genetic loci identified in these two crosses showed exclusive effects on fat deposition, and five loci contributed exclusively to muscle weight. Two additional loci showed pleiotropic effects on fat and muscle weight, with one locus acting in both crosses. Fat weight and muscle weight were influenced by epistatic effects. We provide evidence that significant fat loci in strains selected for body weight contribute to fat weight both directly and indirectly via the influence on lean weight. These results shed new light on the action of genes in quantitative trait locus regions potentially influencing muscle and fat mass and thus controlling body weight as a composite trait.