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Session: Nutrient-Gene Interactions/Precision Nutrition (Oral 36)

(OR36-04-24) Dietary Parent-of-Origin Effects Augment Metabolic Syndrome Susceptibility in the Collaborative Cross

Tuesday, July 2, 2024
10:36 AM – 10:48 AM CT
Location:  W375C

    Presenting Author(s)

  • DB

    Dawson Budke, BS (he/him/his)

    PhD Candidate
    University of California, Davis
    Davis, California, United States

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • BB

    Brian J. Bennett, PhD

    Research Leader, Obesity and Metabolism Unit
    USDA-ARS and UC Davis
    Davis, California, United States

  • PY

    Phoebe Yam, PhD

    Postdoctoral scholar
    USDA
    DAVIS, California, United States

Objectives: Gestation plays a crucial role in a child’s predisposition towards developing metabolic diseases. Genetics influences the effects of maternal diet on offspring susceptibility to Metabolic syndrome (MetSyn). Parent-of-Origin effects (POE) are underexamined in the context of maternal diet’s influence on transgenerational MetSyn development, and experiments in genetic reference panels may aid our understanding of POE influence on gene:diet interactions during gestation. This study examines how a maternal low protein (LP) diet and POE influence offspring MetSyn phenotypes in Collaborative Cross (CC) mice.

Methods: Three CC strains, a multiparental recombinant inbred panel emulating a genetically reproducible heterogeneous population, were selected: CC001, CC0019, and CC040. The CC dams were randomly placed on a 5-week dietary intervention with either control AIN-93G diet or modified AIN-93G LP diet. After two weeks, CC sires were introduced for reciprocal cross breeding. Approximately 21 days later, all dams were placed on AIN-93G diet as they weaned offspring. During the pup’s 4th and 8th weeks, their body composition and weight (BW) were recorded. Pup euthanasia occurred at 8 weeks where blood and tissue samples were collected. Adiposity was measured via an EchoMRI. Data were analyzed by Student’s T-tests, linear mixed model, and Tukey’s Posthoc analyses.

Results: Maternal LP diet erratically modulates offspring MetSyn susceptibility suggesting that genetics and POE are principle confounding pathophysiological variables. All MetSyn phenotypes are markedly influenced by strain genetics indicating that genetic susceptibility is an important determinant of gestational nutrient need. At week 4 on both maternal diets, pup BF% from the CC001xCC019 and CC019xCC040 crosses is lower than pup BF% from their reciprocal crosses. This CC001xCC019 cross POE persists through week 8 (p < 0.01). Interestingly, the CC001xCC019 cross has higher HDL than its reciprocal cross. Numerous diet effects are augmented by POE. For example, CC019xCC001 cross has greater BW and lean mass on the AIN93G than LP diet.

Conclusions: The effect of diet is likely dependent on the underlying parental genetics. POE and POE:diet effects influence the metabolic health of offspring.

Funding Sources: This research was supported by a National Institute of Food and Agriculture grant.