Patient-Oriented and Epidemiological Research
The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men

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Fasting promotes triglyceride (TG) accumulation in lean tissues of some animals, but the effect in humans is unknown. Additionally, fasting lipolysis is sexually dimorphic in humans, suggesting that lean tissue TG accumulation and metabolism may differ between women and men. This study investigated lean tissue TG content and metabolism in women and men during extended fasting. Liver and muscle TG content were measured by magnetic resonance spectroscopy during a 48-h fast in healthy men and women. Whole-body and hepatic carbohydrate, lipid, and energy metabolism were also evaluated using biochemical, calorimetric, and stable isotope tracer techniques. As expected, postabsorptive plasma fatty acids (FAs) were higher in women than in men but increased more rapidly in men with the onset of early starvation. Concurrently, sexual dimorphism was apparent in lean tissue TG accumulation during the fast, occurring in livers of men but in muscles of women. Despite differences in lean tissue TG distribution, men and women had identical fasting responses in whole-body and hepatic glucose and oxidative metabolism. In conclusion, TG accumulated in livers of men but in muscles of women during extended fasting. This sexual dimorphism was related to differential fasting plasma FA concentrations but not to whole body or hepatic utilization of this substrate.

liver fat
muscle fat
magnetic resonance spectroscopy

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This work was supported by the Clinical and Translational Science Award (CTSA) at UT Southwestern (UL1RR024982), the Task Force for Obesity Research (TORS) at UT Southwestern (UL1DE019584), the TORS Human Biology Core (PL1DK081183), and the TORS Molecular and Metabolic Mouse Phenotyping Core (PL1DK081182). This work was also supported by National Institutes of Health Grants RL1DK081187 (J.D.B., S.C.B.), K23DK074396 (J.D.B.), R01DK087977 (J.D.B.), RR02584 (S.C.B.), R01DK078184 (S.C.B.), and ADA7-09-BS-24 (S.C.B.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies.

    Abbreviations

    CTRC

    Clinical and Translational Research Center

    EGP

    endogenous glucose production

    1H-MRS

    proton magnetic resonance spectroscopy

    OAA

    oxaloacetate

    PC

    pyruvate carboxylase

    PEPCK

    phosphoenolpyruvate carboxykinase

    STEAM

    stimulated echo acquisition mode

    TG

    triglyceride