Paternal low protein diet perturbs inter-generational metabolic homeostasis in a tissue-specific manner in mice

Hannah L Morgan, Samuel Furse, Irundika H K Dias, Kiran Shabir, Marcos Castellanos, Iqbal Khan, Sean T May, Nadine Holmes, Matthew Carlile, Fei Sang, Victoria Wright, Albert Koulman, Adam J Watkins

Research output: Contribution to journalArticlepeer-review


The underlying mechanisms driving paternally-programmed metabolic disease in offspring remain poorly defined. We fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. Using artificial insemination, in combination with vasectomised male mating, we generated offspring using either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Offspring from either LPD sperm or seminal fluid display elevated body weight and tissue dyslipidaemia from just 3 weeks of age. These changes become more pronounced in adulthood, occurring in conjunction with altered hepatic metabolic and inflammatory pathway gene expression. Second generation offspring also display differential tissue lipid abundance, with profiles similar to those of first generation adults. These findings demonstrate that offspring metabolic homeostasis is perturbed in response to a suboptimal paternal diet with the effects still evident within a second generation.
Original languageEnglish
Article number929
Number of pages12
JournalCommunications Biology
Issue number1
Publication statusPublished - 8 Sept 2022

Bibliographical note

© 2022, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit

Funding: This work was supported by an Aston Research Centre for Healthy Ageing fellowship and by a Biotechnology and Biological Sciences Research Council (BBSRC) grant (BB/R003556/1) to A.J.W. and also a BBSRC grant (BB/M027252/1) awarded to A.K. to support S.F.


  • Animals
  • Diet, Protein-Restricted
  • Fathers
  • Homeostasis
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Semen


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