Methyl donor supplementation prevents transgenerational amplification of obesity.
Methyl donor supplementation prevents transgenerational amplification of obesity.
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DOI：
10.1038/ijo.2008.100
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发表时间：
2008-09
影响因子：
4.9
通讯作者：
Mirza, S.
中科院分区：
文献类型：
--
作者：
Waterland, R. A.;Travisano, M.;Tahiliani, K. G.;Rached, M. T.;Mirza, S.
几十年来在发达国家被公认的肥胖流行病现在是一个世界性的现象。所有年龄组都受到影响，包括育龄妇女，这加剧了人们的担忧，即孕妇在怀孕和哺乳之前和期间的肥胖会损害胎儿或婴儿体重调节机制的发育建立，导致肥胖患病率和严重程度的代际放大。这些过程背后的生物学机制仍然未知。我们使用无活力的黄（Avy）小鼠来检验母体肥胖诱导肥胖跨代放大的假设。我们通过三代Avy/a雌性传递Avy等位基因，并评估其对毛色和体重的累积效应。通过研究两个独立但同时存在的小鼠群体，一个提供标准饮食，另一个提供在发育过程中诱导DNA超甲基化的甲基补充饮食，我们测试了对体重的潜在跨代影响是否可能由包括DNA甲基化在内的表观遗传机制的改变介导。当Avy等位基因通过连续几代肥胖的Avy雌性传递时，Avy小鼠肥胖的遗传倾向逐渐加剧。这种体重的跨代放大是由promethylation膳食补充剂预防的。重要的是，补充甲基对体重的影响与Avy基因座的表观遗传变化无关，表明该模型可能与人类跨代肥胖直接相关。我们的研究结果表明，在具有肥胖遗传倾向的人群中，母体肥胖的影响在连续几代中积累，使人口分布向成年体重增加的方向转变，并表明表观遗传机制参与了这一过程。
The obesity epidemic, recognized in developed nations for decades, is now a worldwide phenomenon. All age groups are affected, including women of childbearing age, fueling concern that maternal obesity before and during pregnancy and lactation impairs developmental establishment of body weight regulatory mechanisms in the fetus or infant, causing transgenerational amplification of obesity prevalence and severity. The biological mechanisms underlying such processes remain unknown. We used agouti viable yellow (Avy) mice to test the hypothesis that maternal obesity induces transgenerational amplification of obesity. We passed the Avy allele through three generations of Avy/a females and assessed cumulative effects on coat color and body weight. By studying two separate but contemporaneous populations of mice, one provided a standard diet and the other a methyl-supplemented diet that induces DNA hypermethylation during development, we tested whether potential transgenerational effects on body weight might be mediated by alterations in epigenetic mechanisms including DNA methylation. The genetic tendency for obesity in Avy mice was progressively exacerbated when the Avy allele was passed through successive generations of obese Avy females. This transgenerational amplification of body weight was prevented by a promethylation dietary supplement. Importantly, the effect of methyl supplementation on body weight was independent of epigenetic changes at the Avy locus, indicating this model may have direct relevance to human transgenerational obesity. Our results show that in a population with a genetic tendency for obesity, effects of maternal obesity accumulate over successive generations to shift the population distribution toward increased adult body weight, and suggest that epigenetic mechanisms are involved in this process.
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影响因子：
5
作者：
Lawlor, Debbie A.;Smith, George Davey;Najman, Jake M.
通讯作者：
Najman, Jake M.
DOI：
10.1152/ajpregu.1998.275.4.r1374
发表时间：
1998-10-01
影响因子：
2.8
作者：
Levin, BE;Govek, E
通讯作者：
Govek, E
DOI：
10.1152/ajpendo.1995.269.4.e731
发表时间：
1995-10-01
影响因子：
5.1
作者：
VADLAMUDI, S;KALHAN, SC;PATEL, MS
通讯作者：
PATEL, MS
影响因子：
56.9
作者：
WOLFF, GL
通讯作者：
WOLFF, GL
影响因子：
8
作者：
Kral, John G.;Biron, Simon;Marceau, Picard
通讯作者：
Marceau, Picard