Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses.
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 (Ser(485)) (P < 0.01), p-PDPK-1 (Ser(41)) (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.
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia;
Shervi
S
Lie
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia;
Janna L
http://orcid.org/0000-0002-8602-8519
JL
Morrison
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia; Discipline of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, Australia;
Olivia
O
Williams-Wyss
Victor Chang Cardiac Research Institute, Darlinghurst, Australia; Faculty of Medicine, University of New South Wales, Kensington, Australia;
Catherine M
CM
Suter
Victor Chang Cardiac Research Institute, Darlinghurst, Australia;
David T
DT
Humphreys
University of Cambridge, Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom;
Susan E
SE
Ozanne
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia;
Song
S
Zhang
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia;
Severence M
SM
MacLaughlin
South Australian Research and Development Institute, Turretfield Research Centre, Rosedale, Australia;
David O
DO
Kleemann
South Australian Research and Development Institute, Turretfield Research Centre, Rosedale, Australia;
Simon K
SK
Walker
Institute and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia; and.
Claire T
CT
Roberts
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia; The Chancellery, University of Newcastle, Newcastle, Australia caroline.mcmillen@newcastle.edu.au.
I Caroline
IC
McMillen
D000818:Animals; D005260:Female; D005306:Fertilization / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D044342:Malnutrition / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D035683:MicroRNAs; D014157:Transcription Factors; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D017346:Protein Serine-Threonine Kinases
epigenetic; fatty acid; liver; nutrition; pregnancy