Exercise and diet affect quantitative trait loci for body weight and composition traits in an advanced intercross population of mice.

Driven by the recent obesity epidemic, interest in understanding the complex genetic and environmental basis of body weight and composition is great. We investigated this by searching for quantitative trait loci (QTLs) affecting a number of weight and adiposity traits in a G(10) advanced intercross population produced from crosses of mice in inbred strain C57BL/6J with those in a strain selected for high voluntary wheel running. The mice in this population were fed either a high-fat or a control diet throughout the study and also measured for four exercise traits prior to death, allowing us to test for pre- and postexercise QTLs as well as QTL-by-diet and QTL-by-exercise interactions. Our genome scan uncovered a number of QTLs, of which 40% replicated QTLs previously found for similar traits in an earlier (G(4)) generation. For those replicated QTLs, the confidence intervals were reduced from an average of 19 Mb in the G(4) to 8 Mb in the G(10). Four QTLs on chromosomes 3, 8, 13, and 18 were especially prominent in affecting the percentage of fat in the mice. About of all QTLs showed interactions with diet, exercise, or both, their genotypic effects on the traits showing a variety of patterns depending on the diet or level of exercise. It was concluded that the indirect effects of these QTLs provide an underlying genetic basis for the considerable variability in weight or fat loss typically found among individuals on the same diet and/or exercise regimen.

在近期肥胖流行的推动下，人们对了解体重和身体组成的复杂遗传和环境基础有着极大的兴趣。我们通过在一个由近交系C57BL/6J小鼠与一个因高自主转轮运动而被选育的品系小鼠杂交产生的G(10)高级互交群体中寻找影响多种体重和肥胖性状的数量性状位点（QTLs）来对此进行研究。在整个研究过程中，该群体中的小鼠要么被喂食高脂肪饮食，要么被喂食对照饮食，并且在死亡前还对四种运动性状进行了测量，这使我们能够检测运动前和运动后的QTLs以及QTL与饮食和QTL与运动的相互作用。我们的基因组扫描发现了许多QTLs，其中40%重复了在早期（G(4)）代中针对类似性状先前发现的QTLs。对于那些重复的QTLs，置信区间从G(4)中的平均19兆碱基（Mb）减少到G(10)中的8 Mb。在3号、8号、13号和18号染色体上的四个QTLs在影响小鼠脂肪百分比方面尤为显著。大约所有的QTLs都显示出与饮食、运动或两者的相互作用，它们对性状的基因型效应根据饮食或运动水平呈现出多种模式。结论是，这些QTLs的间接效应为在相同饮食和/或运动方案下个体之间通常存在的体重或脂肪减少的显著差异提供了潜在的遗传基础。