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

• Published in: International journal of molecular sciences 2023-01, Vol.24 (3), p.1814
• Main Authors: Furse, Samuel, Morgan, Hannah L, Koulman, Albert, Watkins, Adam J
• Format: Article
• Language: English
• Subjects: Adults; Age; Animals; Artificial insemination; Brain; Carbohydrates; Cardiovascular disease; Cardiovascular diseases; developmental programming; Diabetes; Diabetes mellitus; Diet; Female; Heart; High carbohydrate diet; High protein diet; Homeostasis; Insulin; lipid homeostasis; Lipids; Low carbohydrate diet; Low protein diet; Male; Males; metabolic disorder; Metabolic disorders; Metabolism; Mice; Mice, Inbred C57BL; Nutrient deficiency; Obesity; paternal diet; Plasma; Principal components analysis; Proteins; Reproduction (biology); Scientific imaging; Semen; semen quality; Seminal fluid; Sperm; Triglycerides
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24031814

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.