Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity

Cropley, JE; Eaton, SA; Aiken, A; Young, PE; Giannoulatou, E; Ho, JWK; Buckland, ME; Keam, SP; Hutvagner, G; Humphreys, DT; Langley, KG; Henstridge, DC; Martin, DIK; Febbraio, MA; Suter, CM

Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity

Cropley, JE Eaton, SA Aiken, A Young, PE Giannoulatou, E Ho, JWK Buckland, ME Keam, SP Hutvagner, G

Humphreys, DT Langley, KG Henstridge, DC Martin, DIK Febbraio, MA Suter, CM

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Publication Type:: Journal Article
Citation:: Molecular Metabolism, 2016, 5 (8), pp. 699 - 708
Issue Date:: 2016-08-01

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Field	Value	Language
dc.contributor.author	Cropley, JE	en_US
dc.contributor.author	Eaton, SA	en_US
dc.contributor.author	Aiken, A	en_US
dc.contributor.author	Young, PE	en_US
dc.contributor.author	Giannoulatou, E	en_US
dc.contributor.author	Ho, JWK	en_US
dc.contributor.author	Buckland, ME	en_US
dc.contributor.author	Keam, SP	en_US
dc.contributor.author	Hutvagner, G https://orcid.org/0000-0002-7231-9446	en_US
dc.contributor.author	Humphreys, DT	en_US
dc.contributor.author	Langley, KG	en_US
dc.contributor.author	Henstridge, DC	en_US
dc.contributor.author	Martin, DIK	en_US
dc.contributor.author	Febbraio, MA	en_US
dc.contributor.author	Suter, CM	en_US
dc.date.available	2016-06-16	en_US
dc.date.issued	2016-08-01	en_US
dc.identifier.citation	Molecular Metabolism, 2016, 5 (8), pp. 699 - 708	en_US
dc.identifier.issn	2212-8778	en_US
dc.identifier.uri	http://hdl.handle.net/10453/50309
dc.description.abstract	© 2016 The Author(s) 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.	en_US
dc.relation	http://purl.org/au-research/grants/arc/DP130103027
dc.relation.ispartof	Molecular Metabolism	en_US
dc.relation.isbasedon	10.1016/j.molmet.2016.06.008	en_US
dc.title	Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	5	en_US
utslib.for	0903 Biomedical Engineering	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0606 Physiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	5	en_US

Abstract:

© 2016 The Author(s) 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.

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http://hdl.handle.net/10453/50309