Research press release


Nature Genetics

Non-genetic inheritance of diet-induced obesity in mice



今回、P Huypens、J Beckersたちの研究グループは、遺伝学的に同一なマウスに対し、6週間にわたって高脂肪食、低脂肪食または通常食を与えた。高脂肪食を与えられたマウスは、予想通り、肥満と耐糖能異常になった。次に、Huypensたちは、異なった食餌を与えられたマウスの精子と卵を組み合わせてさまざまな初期胚を作製し、健康な代理母に移植することで、精子や卵のみに存在するエピジェネティック因子から環境因子を排除した。そして生まれた仔が成体になったところで高脂肪食を与えた。肥満の両親から生まれた仔は、両親の一方のみが肥満の場合よりも体重増が顕著だった。また、いずれの両親も肥満でない場合が、高脂肪食による体重増が最も少なかった。これと類似したパターンが耐糖能異常についても見られ、Huypensたちは、配偶子に含まれるエピジェネティック因子が親から仔へ肥満と糖尿病のリスクが伝わる上で重要な役割を担っていると結論づけている。

Epigenetic factors transmitted in mice through the sperm and eggs (gametes) predispose the offspring of obese parents to diet-induced obesity, reports a paper published online this week in Nature Genetics. The study shows a direct role for epigenetic effects without the confounding effects of environment.

In addition to passing on genetic information to their offspring in the form of DNA, parents may also pass on epigenetic modifications to their genetic material - reversible alterations that affect gene expression but do not change the DNA sequence - that they acquire throughout their lives. Epidemiological and model organism studies suggest that an individual’s risk of developing obesity can be increased through inherited epigenetic factors. However, whether environmental conditions, such as the mother’s diet during pregnancy or breastfeeding, molecules present in the father’s seminal fluid or parental microbiomes, are responsible for the inheritance of these epigenetic factors has not yet been established.

Peter Huypens, Johannes Beckers and colleagues fed genetically identical mice a high-fat, low-fat or normal diet for six weeks. Mice fed a high-fat diet developed obesity and glucose intolerance, as expected. The authors then produced embryos using combinations of sperm and eggs from the mice fed different diets and implanted the embryos into healthy surrogate mothers, which allowed the authors to separate environmental factors from epigenetic factors present only within the sperm or eggs. The adult offspring were then fed a high-fat diet. Offspring with two obese parents gained significantly more weight on a high-fat diet than those with only one obese parent. Offspring of two lean parents gained the least weight on a high-fat diet. The authors observed similar patterns for glucose intolerance and conclude that epigenetic factors in gametes have an important role in the transmission of obesity and diabetes risk from parents to offspring.

doi: 10.1038/ng.3527

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