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Characterisation of the Paternal Influence on Intergenerational Offspring Cardiac and Brain Lipid Homeostasis in Mice

Furse, Samuel; Morgan, Hannah L.; Koulman, Albert; Watkins, Adam J.

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Authors

Samuel Furse

Hannah L. Morgan

Albert Koulman



Abstract

There is growing evidence that poor paternal diet at the time of conception increase the risk of offspring developing a range of non-communicable metabolic diseases, such as obesity, diabetes and cardiovascular disease, in adulthood. We hypothesise that a paternal low protein–high carbohydrate diet perturbs offspring tissue lipid abundance through both sperm and seminal plasma-mediated mechanisms. To test our hypothesis, 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. We generated offspring through artificial insemination, in combination with vasectomised male mating. Using this approach, we derived offspring from either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Using high resolution mass-spectrometry, we found that offspring derived from either LPD sperm or seminal fluid displayed perturbed cardiac and brain lipid abundance from just three weeks of age, typically associated with the altered abundance of tissue triglycerides. We also observed the differential sex-specific patterns of lipids between the control and experimental offspring’s hearts and brains. These observations indicate that poor paternal diet at the time of conception affects offspring cardiac and brain lipid profiles in an age-, sex- and generation-specific manner.

Citation

Furse, S., Morgan, H. L., Koulman, A., & Watkins, A. J. (2023). Characterisation of the Paternal Influence on Intergenerational Offspring Cardiac and Brain Lipid Homeostasis in Mice. International Journal of Molecular Sciences, 24(3), Article 1814. https://doi.org/10.3390/ijms24031814

Journal Article Type Article
Acceptance Date Jan 11, 2023
Online Publication Date Jan 17, 2023
Publication Date Feb 1, 2023
Deposit Date Jan 18, 2023
Publicly Available Date Jan 18, 2023
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Electronic ISSN 1422-0067
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 24
Issue 3
Article Number 1814
DOI https://doi.org/10.3390/ijms24031814
Keywords Developmental programming; metabolic disorder; paternal diet; semen quality; lipid homeostasis
Public URL https://nottingham-repository.worktribe.com/output/16223182
Publisher URL https://www.mdpi.com/1422-0067/24/3/1814
PMID 36768137

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