Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses
Autor: | David T. Humphreys, Janna L. Morrison, Shervi Lie, David O. Kleemann, Catherine M. Suter, Susan E. Ozanne, Claire T. Roberts, Song Zhang, I. Caroline McMillen, Simon K. Walker, Severence M. MacLaughlin, Olivia Williams-Wyss |
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Přispěvatelé: | Lie, Shervi, Morrison, Janna L, Williams-Wyss, Olivia, Suter, Catherine M, Humphreys, David T, Ozanne, Susan E, Zhang, Song, MacLaughlin, Severence M, Kleemann, David O, Walker, Simon K, Roberts, Claire T, McMillen, I Caroline |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism PDK4 030209 endocrinology & metabolism Protein Serine-Threonine Kinases Biology liver 03 medical and health sciences 0302 clinical medicine Pregnancy Physiology (medical) Internal medicine medicine Animals Beta oxidation chemistry.chemical_classification Fetus Sheep Malnutrition Gene Expression Regulation Developmental Fatty acid Lipid metabolism Embryo Articles Maternal Nutritional Physiological Phenomena Lipid Metabolism medicine.disease MicroRNAs nutrition 030104 developmental biology Endocrinology Liver chemistry Fertilization Gestation Female pregnancy fatty acid Protein Kinases epigenetic Transcription Factors |
Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 310:E148-E159 |
ISSN: | 1522-1555 0193-1849 |
Popis: | 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 β-oxidation in the PCUN and PIUN groups. Therefore, embryo number and the timing of maternal undernutrition in early pregnancy have a differential impact on hepatic microRNA expression and on the factors that regulate hepatic fatty acid oxidation and lipid synthesis. |
Databáze: | OpenAIRE |
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