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

Jennifer E. Cropley, Sally A. Eaton, Alastair Aiken, Paul E. Young, Eleni Giannoulatou, Joshua W.K. Ho, Michael E. Buckland, Simon P. Keam, Gyorgy Hutvagner, David T Humphreys, Katherine G. Langley, Darren C. Henstridge, David I.K. Martin, Mark A. Febbraio, Catherine M Suter

Research output: Contribution to journalArticleResearchpeer-review

56 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)699-708
Number of pages10
JournalMolecular Metabolism
Volume5
Issue number8
DOIs
Publication statusPublished - 1 Aug 2016
Externally publishedYes

Keywords

  • Epigenetic inheritance
  • Noncoding RNA
  • Paternal effects
  • Sperm RNA

Cite this

Cropley, J. E., Eaton, S. A., Aiken, A., Young, P. E., Giannoulatou, E., Ho, J. W. K., ... Suter, C. M. (2016). Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity. Molecular Metabolism, 5(8), 699-708. https://doi.org/10.1016/j.molmet.2016.06.008
Cropley, Jennifer E. ; Eaton, Sally A. ; Aiken, Alastair ; Young, Paul E. ; Giannoulatou, Eleni ; Ho, Joshua W.K. ; Buckland, Michael E. ; Keam, Simon P. ; Hutvagner, Gyorgy ; Humphreys, David T ; Langley, Katherine G. ; Henstridge, Darren C. ; Martin, David I.K. ; Febbraio, Mark A. ; Suter, Catherine M. / Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity. In: Molecular Metabolism. 2016 ; Vol. 5, No. 8. pp. 699-708.
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abstract = "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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author = "Cropley, {Jennifer E.} and Eaton, {Sally A.} and Alastair Aiken and Young, {Paul E.} and Eleni Giannoulatou and Ho, {Joshua W.K.} and Buckland, {Michael E.} and Keam, {Simon P.} and Gyorgy Hutvagner 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}",
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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 2016, 'Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity', Molecular Metabolism, vol. 5, no. 8, pp. 699-708. https://doi.org/10.1016/j.molmet.2016.06.008

Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity. / Cropley, Jennifer E.; Eaton, Sally A.; Aiken, Alastair; Young, Paul E.; Giannoulatou, Eleni; Ho, Joshua W.K.; Buckland, Michael E.; Keam, Simon P.; Hutvagner, Gyorgy; Humphreys, David T; Langley, Katherine G.; Henstridge, Darren C.; Martin, David I.K.; Febbraio, Mark A.; Suter, Catherine M.

In: Molecular Metabolism, Vol. 5, No. 8, 01.08.2016, p. 699-708.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity

AU - Cropley, Jennifer E.

AU - Eaton, Sally A.

AU - Aiken, Alastair

AU - Young, Paul E.

AU - Giannoulatou, Eleni

AU - Ho, Joshua W.K.

AU - Buckland, Michael E.

AU - Keam, Simon P.

AU - Hutvagner, Gyorgy

AU - Humphreys, David T

AU - Langley, Katherine G.

AU - Henstridge, Darren C.

AU - Martin, David I.K.

AU - Febbraio, Mark A.

AU - Suter, Catherine M

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

KW - Epigenetic inheritance

KW - Noncoding RNA

KW - Paternal effects

KW - Sperm RNA

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