Selman Colin, Hempenstall Sarah
Integrative and Environmental Physiology, Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen,, AB24 2TZ, UK.
Longev Healthspan. 2012 Sep 3;1:2. doi: 10.1186/2046-2395-1-2. eCollection 2012.
Dietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals. What is far less clear is whether animals retain a metabolic memory to previous DR exposure, that is, can early-life DR preserve beneficial metabolic effects later in life even after the resumption of ad libitum (AL) feeding. We examined a range of metabolic parameters (body mass, body composition (lean and fat mass), glucose tolerance, fed blood glucose, fasting plasma insulin and insulin-like growth factor 1 (IGF-1), insulin sensitivity) in male C57BL/6 mice dietary switched from DR to AL (DR-AL) at 11 months of age (mid life). The converse switch (AL-DR) was also undertaken at this time. We then compared metabolic parameters of the switched mice to one another and to age-matched mice maintained exclusively on an AL or DR diet from early life (3 months of age) at 1 month, 6 months or 10 months post switch.
Male mice dietary switched from AL-DR in mid life adopted the metabolic phenotype of mice exposed to DR from early life, so by the 10-month timepoint the AL-DR mice overlapped significantly with the DR mice in terms of their metabolic phenotype. Those animals switched from DR-AL in mid life showed clear evidence of a glycemic memory, with significantly improved glucose tolerance relative to mice maintained exclusively on AL feeding from early life. This difference in glucose tolerance was still apparent 10 months after the dietary switch, despite body mass, fasting insulin levels and insulin sensitivity all being similar to AL mice at this time.
Male C57BL/6 mice retain a long-term glycemic memory of early-life DR, in that glucose tolerance is enhanced in mice switched from DR-AL in mid life, relative to AL mice, even 10 months following the dietary switch. These data therefore indicate that the phenotypic benefits of DR are not completely dissipated following a return to AL feeding. The challenge now is to understand the molecular mechanisms underlying these effects, the time course of these effects and whether similar interventions can confer comparable benefits in humans.
饮食限制（DR）可延长许多动物的寿命并诱导有益的代谢效应。但目前尚不清楚的是，动物是否会保留对先前DR暴露的代谢记忆，也就是说，早年的DR能否在恢复自由采食（AL）后仍在生命后期保持有益的代谢效应。我们检测了11月龄（中年）从DR转换为AL饮食（DR-AL）的雄性C57BL/6小鼠的一系列代谢参数（体重、身体组成（瘦体重和脂肪量）、葡萄糖耐量、进食血糖、空腹血浆胰岛素和胰岛素样生长因子1（IGF-1）、胰岛素敏感性）。同时也进行了相反的转换（AL-DR）。然后，我们将转换后的小鼠的代谢参数相互比较，并与从生命早期（3月龄）开始就一直只食用AL或DR饮食的年龄匹配小鼠在转换后1个月、6个月或10个月时进行比较。
中年从AL-DR转换饮食的雄性小鼠采用了从生命早期就暴露于DR的小鼠的代谢表型，因此到10个月时间点时，AL-DR小鼠在代谢表型方面与DR小鼠有显著重叠。那些中年从DR-AL转换的动物表现出明显的血糖记忆证据，相对于从生命早期就一直只食用AL的小鼠，其葡萄糖耐量显著改善。尽管在饮食转换10个月后体重、空腹胰岛素水平和胰岛素敏感性此时都与AL小鼠相似，但这种葡萄糖耐量的差异仍然明显。
雄性C57BL/6小鼠保留了对早年DR的长期血糖记忆，即相对于AL小鼠，中年从DR-AL转换的小鼠的葡萄糖耐量增强，即使在饮食转换后10个月也是如此。因此，这些数据表明，恢复AL喂养后，DR的表型益处并未完全消失。现在面临的挑战是了解这些效应背后的分子机制、这些效应的时间进程以及类似的干预措施是否能在人类中带来类似的益处。
