Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice.
Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice.
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DOI：
10.1186/2046-2395-1-2
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Hempenstall S
中科院分区：
文献类型：
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作者：
Selman C;Hempenstall S
饮食限制(DR)延长了许多动物的寿命并诱导了有益的新陈代谢效应。目前尚不清楚的是，动物是否对之前的DR暴露保持了代谢记忆，即早期DR是否能在以后的生活中保留有益的代谢效应，即使在恢复自由摄食(AL)之后也是如此。我们检测了11 月龄(中年)从DR饮食转换为AL(DR-AL)的雄性C57BL/6小鼠的一系列代谢参数(体质量、体组成(瘦体重和脂肪质量)、糖耐量、喂养血糖、空腹血浆胰岛素和胰岛素样生长因子1、胰岛素敏感性)。此时也进行了反向转换(AL-DR)。然后，我们比较了切换的小鼠之间的代谢参数，以及切换后1 月、6 月或10 月的早期(3 月龄)完全以AL或DR饮食维持的年龄匹配小鼠的代谢参数。在中年从AL-DR转变的雄性小鼠采用了早期暴露于DR的代谢表型，因此在10个月的时间点，AL-DR小鼠的代谢表型与DR小鼠显著重叠。那些在中年从DR-AL转换而来的动物显示出明显的血糖记忆，与早期只喂食AL的小鼠相比，它们的葡萄糖耐量显著改善。尽管此时体重、空腹胰岛素水平和胰岛素敏感性都与AL小鼠相似，但在饮食改变10个 月后，这种葡萄糖耐量的差异仍然明显。雄性C57BL/6小鼠保留了早期DR的长期血糖记忆，因为在中年从DR-AL转换的小鼠的葡萄糖耐量比AL小鼠更高，即使在饮食转换后10个 月也是如此。因此，这些数据表明，在恢复饲喂AL后，DR的表型益处并未完全消失。现在的挑战是了解这些影响背后的分子机制，这些影响的时间进程，以及类似的干预是否可以在人类身上带来类似的好处。
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.