Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses

Shervi Lie, Janna Morrison, Olivia Williams-Wyss, Catherine Suter, David Humphreys, Susan Ozanne, Song Zhang, Severence MacLaughlin, David Kleemann, Simon Walker, Claire T Roberts, I Caroline McMillen

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    6 Citations (Scopus)

    Abstract

    We have investigated the effects of embryo number and maternal undernutrition imposed either around the time of conception or before implantation on hepatic lipid metabolism in the sheep fetus. We have demonstrated that periconceptional undernutrition and preimplantation undernutrition each resulted in decreased hepatic fatty acid β-oxidation regulators, PGC-1α (P < 0.05), PDK2 (P < 0.01), and PDK4 (P < 0.01) mRNA expression in singleton and twin fetuses at 135-138 days gestation. In singletons, there was also lower hepatic PDK4 (P < 0.01), CPT-1 (P < 0.01), and PKCζ (P < 0.01) protein abundance in the PCUN and PIUN groups and a lower protein abundance of PDPK-1 (P < 0.05) in the PCUN group. Interestingly, in twins, the hepatic protein abundance of p-AMPK (Ser485) (P < 0.01), p-PDPK-1 (Ser41) (P < 0.05), and PKCζ (P < 0.05) was higher in the PCUN and PIUN groups, and hepatic PDK4 (P < 0.001) and CPT-1 (P < 0.05) protein abundance was also higher in the PIUN twin fetus. We also found that the expression of a number of microRNAs was altered in response to PCUN or PIUN and that there is evidence that these changes may underlie the changes in the protein abundance of key regulators of hepatic fatty acid ²-oxidation in the PCUN and PIUN groups. Therefore, embryo number and the timing of maternal undernutrition in early pregnancy have a differential impact on he- patic microRNA expression and on the factors that regulate hepatic fatty acid oxidation and lipid synthesis.

    Original languageEnglish
    Pages (from-to)E148-E159
    Number of pages12
    JournalAm J Physiol Endocrinol Metab
    Volume310
    Issue number2
    DOIs
    Publication statusPublished - 2016

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