期刊
MOLECULAR METABOLISM
卷 5, 期 8, 页码 699-708出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molmet.2016.06.008
关键词
Paternal effects; Epigenetic inheritance; Noncoding RNA; Sperm RNA
Objective: Parental obesity can induce metabolic phenotypes in offspring independent of the inherited DNA sequence. Here we asked whether such non-genetic acquired metabolic traits can be passed on to a second generation that has never been exposed to obesity, even as germ cells. Methods: We examined the F1, F2, and F3 a/a offspring derived from F0 matings of obese prediabetic A(vy)/a sires and lean a/a dams. After F0, only lean a/a mice were used for breeding. Results: We found that F1 sons of obese founder males exhibited defects in glucose and lipid metabolism, but only upon a post-weaning dietary challenge. F1 males transmitted these defects to their own male progeny (F2) in the absence of the dietary challenge, but the phenotype was largely attenuated by F3. The sperm of F1 males exhibited changes in the abundance of several small RNA species, including the recently reported diet-responsive tRNA-derived fragments. Conclusions: These data indicate that induced metabolic phenotypes may be propagated for a generation beyond any direct exposure to an inducing factor. This non-genetic inheritance likely occurs via the actions of sperm noncoding RNA. (C) 2016 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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