Abstract
Recent evidence obtained from a rodent model of birth asphyxia shows that supplementation of the maternal diet with creatine during pregnancy protects the neonate from multi-organ damage. However, the effect of increasing creatine intake on creatine homeostasis and biosynthesis in females, particularly during pregnancy, is unknown. This study assessed the impact of creatine supplementation on creatine homeostasis, body composition, capacity for de novo creatine synthesis and renal excretory function in non-pregnant and pregnant spiny mice. Mid-gestation pregnant and virgin spiny mice were fed normal chow or chow supplemented with 5 % w/w creatine for 18 days. Weight gain, urinary creatine and electrolyte excretion were assessed during supplementation. At post mortem, body composition was assessed by Dual-energy X-ray absorptiometry, or tissues were collected to assess creatine content and mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) and the creatine transporter (CrT1). Protein expression of AGAT and GAMT was also assessed by Western blot. Key findings of this study include no changes in body weight or composition with creatine supplementation; increased urinary creatine excretion in supplemented spiny mice, with increased sodium (P < 0.001) and chloride (P < 0.05) excretion in pregnant dams after 3 days of supplementation; lowered renal AGAT mRNA (P < 0.001) and protein (P < 0.001) expressions, and lowered CrT1 mRNA expression in the kidney (P < 0.01) and brain (P < 0.001). Creatine supplementation had minimal impact on creatine homeostasis in either non-pregnant or pregnant spiny mice. Increasing maternal dietary creatine consumption could be a useful treatment for birth asphyxia.
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Acknowledgments
Funding from the National Health and Medical Research Council of Australia (APP1047504) to HD, DWW and RJS, the Cerebral Palsy Alliance to HD and DWW, and the Victorian Government’s Operational Infrastructure Support Program supported this work. HD is an NHMRC Career Development Fellow. SJE and DAL were supported by APA Scholarships during the completion of this study. DWW is supported by Cerebral Palsy Alliance and MMK was supported by a National Heart Foundation of Australia Fellowship at the time of this study.
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All spiny mouse experiments were approved in advance by Monash University Animal Ethics Committee (MMCA2010/26) and conducted in accordance with the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes. All listed authors have read the final version of this manuscript and provide consent for publication.
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Ellery, S.J., LaRosa, D.A., Kett, M.M. et al. Dietary creatine supplementation during pregnancy: a study on the effects of creatine supplementation on creatine homeostasis and renal excretory function in spiny mice. Amino Acids 48, 1819–1830 (2016). https://doi.org/10.1007/s00726-015-2150-7
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DOI: https://doi.org/10.1007/s00726-015-2150-7