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Non-genetic inheritance of diet-induced obesity in mice Embargo London: Monday 14 March 2016 16:00 (GMT) New York: Monday 14 March 2016 12:00 (EDT) Tokyo: Tuesday 15 March 2016 01:00 (JST) Sydney: Tuesday 15 March 2016 03:00 (AEDT) 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 inNature 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, lowfat 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. Article and author details 1. Epigenetic germline inheritance of diet-induced obesity and insulin resistance Corresponding Authors Peter Huypens, Neuherberg Helmholtz Zentrum München, Neuherberg, Germany Email: [email protected] Johannes Beckers, Neuherberg Helmholtz Zentrum München, Neuherberg, Germany Email: [email protected], Tel: +49 89 3187 3513 DOI 10.1038/ng.3527 Online paper* http://nature.com/articles/doi:10.1038/ng.3527 * Please link to the article in online versions of your report (the URL will go live after the embargo ends). Geographical listings of authors Germany