Cropley, JE and Eaton, SA and Aiken, A and Young, PE and Giannoulatou, E and Ho, JWK and Buckland, ME and Keam, SP and Hutvagner, G and Humphreys, DT and Langley, KG and Henstridge, DC and Martin, DIK and Febbraio, MA and Suter, CM, Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity, Molecular Metabolism, 5, (8) pp. 699-708. ISSN 2212-8778 (2016) [Refereed Article]
Copyright 2016 The Authors. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/
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 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:||Refereed Article|
|Keywords:||epigenetic inheritance, noncoding RNA, paternal effects, sperm RNA, insulin, transfer RNA, animal cell, animal experiment, breeding, controlled study, dietary intake, disease predisposition, disease transmission, down regulation, female|
|Research Division:||Biological Sciences|
|Research Group:||Biochemistry and cell biology|
|Research Field:||Cell metabolism|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Henstridge, DC (Mr Darren Henstridge)|
|Web of Science® Times Cited:||89|
|Deposited By:||Health Sciences|
|Downloads:||9 View Download Statistics|
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