Cropley, Jennifer E and Eaton, Sally A and Aiken, Alastair and Young, Paul E and Giannoulatou, Eleni and Ho, Joshua W K and Buckland, Michael E and Keam, Simon P and Hutvagner, Gyorgy and Humphreys, David T and Langley, Katherine G and Henstridge, Darren C and Martin, David I K and Febbraio, Mark A and Suter, Catherine M (2016) Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity. Molecular Metabolism, 5 (8). pp.699-708. ISSN 2212-8778 (OA)
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Abstract
AbstractObjective 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 Avy/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.
| Item Type: | Article |
|---|---|
| Additional Information: | 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/). DOAJ |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 21 Jul 2016 23:59 |
| Last Modified: | 28 Sep 2016 04:57 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/470 |
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