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Early onset of fatty liver in growth-restricted rat fetuses and newborns

Authors

  • Makiko Yamada,

    Corresponding author
    1. Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
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  • Diana Wolfe,

    1. Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
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  • Guang Han,

    1. Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
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  • Samuel W. French,

    1. Department of Pathology, Harbor-UCLA Medical Center, Torrance, California, USA
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  • Michael G. Ross,

    1. Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
    2. Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles (UCLA)
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  • Mina Desai

    1. Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
    2. Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles (UCLA)
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Makiko Yamada, MD, PhD, Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA. Email: makiyamd@gmail.com

ABSTRACT

Intrauterine growth-restricted (IUGR) newborns have increased risk of adult metabolic syndrome, including fatty liver. However, it is unclear whether the fatty liver development is “programmed” or secondary to the accompanying obesity. In this study, we examined hepatic lipid accumulation and lipid-regulatory factors (sterol regulatory element-binding protein-1c and fatty acid synthase) in IUGR and Control fetal (embryonic day 20; e20) and newborn (postnatal day 1; p1) rat pups. Notably, despite of in utero undernutrition state, IUGR fetuses demonstrated “fatty liver” with upregulation of these lipogenic indices at as early as e20. Both IUGR and Control newborns exhibited the same extent of massive increase in hepatic lipid content, whereas IUGR newborns continued to exhibit upregulated lipogenic indices. The persistent upregulation of the lipogenic indices in fetal and newborn IUGR suggests that fatty liver is gestationally programmed. Our study suggested that IUGR offspring were born with an altered metabolic life strategy of increased fuel/lipid storage which could be a distinct metabolic pathway of the thrifty phenotype.

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