Skip to main content
NUTRITION 2023 Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Back

Session: Molecular Adaptations to Exercise and Nutrition Interventions (Oral 6)

(OR06-02-23) REDD1 Deletion and Treadmill Running Increase Liver Hepcidin and Gluconeogenic Enzymes in Male Mice

Sunday, July 23, 2023
8:12 AM – 8:24 AM ET
Location:  Commonwealth

    Presenting Author(s)

  • David E. Barney, PhD

    Postdoctoral Researcher
    Pennington Biomedical Research Center, ORISE Participant Supporting USARIEM
    Baton Rouge, Louisiana, United States

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

    • Co-Author(s)

  • BG

    Bradley S. Gordon, PhD

    Florida State University

  • SH

    Stephen R. Hennigar, PhD, PhD

    Pennington Biomedical Research Center

Disclosure(s):
David E. Barney, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: The iron regulatory hormone hepcidin is transcriptionally upregulated by gluconeogenic signals. Recent evidence supports that increases in circulating hepcidin decrease dietary iron absorption following prolonged exercise, however evidence is limited on whether gluconeogenic signals contribute to post-exercise hepcidin. Mice with genetic knockout of regulated in development and DNA response-1 (REDD1) display greater glycogen depletion following exercise, possibly indicating greater gluconeogenesis. The objective of this study was to determine liver hepcidin, markers of gluconeogenesis, and iron metabolism in REDD1 knockout and wildtype mice following prolonged exercise.

Methods: Twelve-week-old male REDD1 knockout and wildtype mice were randomized to rest or 60 min treadmill running with 1, 3, or 6 h recovery (n=5-8/genotype/group). Liver gene expression of hepcidin (Hamp) and gluconeogenic enzymes (Ppargc1a, Creb3l3, Pck1, Pygl) were determined by qRT-PCR. Effects of genotype, exercise, and their interaction were assessed by two-way ANOVAs with Tukey’s post-hoc tests, and Pearson correlations were used to assess the relationships between Hamp and study outcomes.

Results: Liver Hamp increased 1- and 4-fold at 3 and 6 h post-exercise, compared to rest (P-adjusted < 0.009 for all), and was 50% greater in REDD1 knockout compared to wildtype mice (P=0.0015). Liver Ppargc1a, Creb3l3, and Pck1 increased with treadmill running (P < 0.0001 for all), and liver Ppargc1a, Pck1, and Pygl were greater with REDD1 deletion (P < 0.02 for all). Liver Hamp was positively correlated with liver Creb3l3 (R=0.62, P < 0.0001) and Pck1 (R=0.44, P=0.0014).

Conclusions: In conclusion, REDD1 deletion and prolonged treadmill running increased liver Hamp and gluconeogenic regulators of Hamp, suggesting gluconeogenic signaling of hepcidin with prolonged exercise.

Funding Sources: Start-up funds to BSG and SRH.