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Chronic intake of high dietary sucrose induces sexually dimorphic metabolic adaptations in mouse liver and adipose tissue

Author

Listed:
  • Erin J. Stephenson

    (Midwestern University
    University of Tennessee Health Science Center
    Le Bonheur Children’s Hospital)

  • Amanda S. Stayton

    (University of Tennessee Health Science Center
    Le Bonheur Children’s Hospital)

  • Aarti Sethuraman

    (University of Tennessee Health Science Center
    Le Bonheur Children’s Hospital)

  • Prahlad K. Rao

    (University of Tennessee Health Science Center
    Le Bonheur Children’s Hospital)

  • Alice Meyer

    (Midwestern University)

  • Charles Klazer Gomes

    (University of Tennessee Health Science Center)

  • Molly C. Mulcahy

    (University of Michigan School of Public Health)

  • Liam McAllan

    (University of Tennessee Health Science Center
    Le Bonheur Children’s Hospital)

  • Michelle A. Puchowicz

    (University of Tennessee Health Science Center
    Le Bonheur Children’s Hospital)

  • Joseph F. Pierre

    (University of Tennessee Health Science Center
    Le Bonheur Children’s Hospital
    University of Tennessee Health Science Center
    University of Wisconsin-Madison)

  • Dave Bridges

    (University of Tennessee Health Science Center
    Le Bonheur Children’s Hospital
    University of Michigan School of Public Health
    University of Tennessee Health Science Center)

  • Joan C. Han

    (University of Tennessee Health Science Center
    Le Bonheur Children’s Hospital
    University of Tennessee Health Science Center
    Icahn School of Medicine at Mount Sinai and Kravis Children’s Hospital)

Abstract

Almost all effective treatments for non-alcoholic fatty liver disease (NAFLD) involve reduction of adiposity, which suggests the metabolic axis between liver and adipose tissue is essential to NAFLD development. Since excessive dietary sugar intake may be an initiating factor for NAFLD, we have characterized the metabolic effects of liquid sucrose intake at concentrations relevant to typical human consumption in mice. We report that sucrose intake induces sexually dimorphic effects in liver, adipose tissue, and the microbiome; differences concordant with steatosis severity. We show that when steatosis is decoupled from impairments in insulin responsiveness, sex is a moderating factor that influences sucrose-driven lipid storage and the contribution of de novo fatty acid synthesis to the overall hepatic triglyceride pool. Our findings provide physiologic insight into how sex influences the regulation of adipose-liver crosstalk and highlight the importance of extrahepatic metabolism in the pathogenesis of diet-induced steatosis and NAFLD.

Suggested Citation

  • Erin J. Stephenson & Amanda S. Stayton & Aarti Sethuraman & Prahlad K. Rao & Alice Meyer & Charles Klazer Gomes & Molly C. Mulcahy & Liam McAllan & Michelle A. Puchowicz & Joseph F. Pierre & Dave Brid, 2022. "Chronic intake of high dietary sucrose induces sexually dimorphic metabolic adaptations in mouse liver and adipose tissue," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33840-6
    DOI: 10.1038/s41467-022-33840-6
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    References listed on IDEAS

    as
    1. Hongwei Chen & Jue Wang & Zheng Li & Christopher Wai Kei Lam & Ying Xiao & Qibiao Wu & Wei Zhang, 2019. "Consumption of Sugar-Sweetened Beverages Has a Dose-Dependent Effect on the Risk of Non-Alcoholic Fatty Liver Disease: An Updated Systematic Review and Dose-Response Meta-Analysis," IJERPH, MDPI, vol. 16(12), pages 1-13, June.
    2. Grolemund, Garrett & Wickham, Hadley, 2011. "Dates and Times Made Easy with lubridate," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 40(i03).
    3. Ren Lin & Yue Jia & Fengjuan Wu & Yuan Meng & Qi Sun & Lihong Jia, 2019. "Combined Exposure to Fructose and Bisphenol A Exacerbates Abnormal Lipid Metabolism in Liver of Developmental Male Rats," IJERPH, MDPI, vol. 16(21), pages 1-13, October.
    4. Bates, Douglas & Mächler, Martin & Bolker, Ben & Walker, Steve, 2015. "Fitting Linear Mixed-Effects Models Using lme4," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 67(i01).
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