Breeding Biology and Molecular Genetics, Department for Crop and Animal Sciences, Humboldt-Universität zu Berlin, Berlin, Germany; and.
Physiol Genomics. 2013 Sep 16;45(18):817-26. doi: 10.1152/physiolgenomics.00058.2013. Epub 2013 Aug 6.
Obesity, a state of imbalance between lean mass and fat mass, is important for the etiology of diseases affected by the interplay of multiple genetic and environmental factors. Although genome-wide association studies have repeatedly associated genes with obesity and body weight, the mechanisms underlying the interaction between the muscle and adipose tissues remain unknown. Using 351 mice (at 10 wk of age) of an intercross population between Berlin Fat Mouse Inbred (BFMI) and C57BL/6NCrl (B6N) mice, we examined the causal relationships between genetic variations and multiple traits: body lean mass and fat mass, adipokines, and bone mineral density. Furthermore, evidence from structural equation modeling suggests causality among these traits. In the BFMI model, juvenile obesity affects lean mass and impairs bone mineral density via adipokines secreted from the white adipose tissues. While previous studies have indicated that lean mass has a causative effect on adiposity, in the Berlin Fat Mouse model that has been selected for juvenile obesity (at 9 wk of age) for >90 generations, however, the causality is switched from fat mass to lean mass. In addition, linkage studies and statistical modeling have indicated that quantitative trait loci on chromosomes 5 and 6 affect both lean mass and fat mass. These lines of evidence indicate that the muscle and adipose tissues interact with one another and the interaction is modulated by genetic variations that are shaped by selections. Experimental examinations are necessary to verify the biological role of the inferred causalities.
肥胖是指瘦体重和脂肪量之间的失衡状态，对于受多种遗传和环境因素相互作用影响的疾病的病因学很重要。尽管全基因组关联研究已经多次将基因与肥胖和体重联系起来，但肌肉和脂肪组织之间相互作用的机制仍不清楚。我们使用了柏林肥胖小鼠近交系（BFMI）和 C57BL/6NCrl（B6N）杂交种群的 351 只（10 周龄）小鼠，研究了遗传变异与多个特征（体瘦肉量和体脂肪量、脂肪因子和骨矿物质密度）之间的因果关系。此外，结构方程模型的证据表明这些特征之间存在因果关系。在 BFMI 模型中，青少年肥胖通过白色脂肪组织分泌的脂肪因子影响瘦体重并损害骨矿物质密度。虽然先前的研究表明瘦体重对肥胖有因果影响，但在已经选择了 90 多代青少年肥胖（9 周龄）的柏林肥胖小鼠模型中，因果关系从脂肪量切换到了瘦体重。此外，连锁研究和统计建模表明，染色体 5 和 6 上的数量性状基因座影响瘦体重和脂肪量。这些证据表明，肌肉和脂肪组织相互作用，相互作用受到遗传变异的调节，这些遗传变异是由选择形成的。需要进行实验研究来验证推断出的因果关系的生物学作用。
