Swindell William R, List Edward O, Berryman Darlene E, Kopchick John J
Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
Aging (Albany NY). 2018 Apr 29;10(4):701-746. doi: 10.18632/aging.101424.
Caloric restriction (CR) has been extensively studied in rodents as an intervention to improve lifespan and healthspan. However, effects of CR can be strain- and species-specific. This study used publically available microarray data to analyze expression responses to CR in males from 7 mouse strains (C57BL/6J, BALB/c, C3H, 129, CBA, DBA, B6C3F1) and 4 tissues (epididymal white adipose tissue (eWAT), muscle, heart, cortex). In each tissue, the largest number of strain-specific CR responses was identified with respect to the C57BL/6 strain. In heart and cortex, CR responses in C57BL/6 mice were negatively correlated with responses in other strains. Strain-specific CR responses involved genes associated with olfactory receptors (, ) and insulin/IGF-1 signaling (, ). In each strain, CR responses in eWAT were negatively correlated with those in human subcutaneous WAT (scWAT). In human scWAT, CR increased expression of genes associated with stem cell maintenance and vascularization. However, orthologous genes linked to these processes were down-regulated in mouse. These results identify strain-specific CR responses limiting generalization across mouse strains. Differential CR responses in mouse versus human WAT may be due to differences in the depots examined and/or the presence of "thrifty genes" in humans that resist adipose breakdown despite caloric deficit.
热量限制（CR）作为一种改善寿命和健康寿命的干预措施，已在啮齿动物中得到广泛研究。然而，CR的影响可能因品系和物种而异。本研究利用公开的微阵列数据，分析了7种小鼠品系（C57BL/6J、BALB/c、C3H、129、CBA、DBA、B6C3F1）的雄性小鼠以及4种组织（附睾白色脂肪组织（eWAT）、肌肉、心脏、皮质）对CR的表达反应。在每个组织中，相对于C57BL/6品系，鉴定出的品系特异性CR反应数量最多。在心脏和皮质中，C57BL/6小鼠的CR反应与其他品系的反应呈负相关。品系特异性CR反应涉及与嗅觉受体（，）和胰岛素/IGF-1信号传导（，）相关的基因。在每个品系中，eWAT中的CR反应与人类皮下脂肪组织（scWAT）中的反应呈负相关。在人类scWAT中，CR增加了与干细胞维持和血管生成相关基因的表达。然而，与这些过程相关的直系同源基因在小鼠中被下调。这些结果确定了品系特异性CR反应限制了在小鼠品系间的普遍适用性。小鼠与人类脂肪组织中CR反应的差异可能是由于所检查的脂肪库不同和/或人类中存在“节俭基因”，尽管热量不足仍能抵抗脂肪分解。
