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Open AccessArticle

Methyl Donor Deficiency during Gestation and Lactation in the Rat Affects the Expression of Neuropeptides and Related Receptors in the Hypothalamus

Inserm U1256, Faculté de Médecine, Université de Lorraine, 9 avenue de la Forêt de Haye, F-54500 Vandoeuvre-lès-Nancy, France
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These authors contributed equally to the work.
Int. J. Mol. Sci. 2019, 20(20), 5097; https://doi.org/10.3390/ijms20205097
Received: 30 August 2019 / Revised: 4 October 2019 / Accepted: 12 October 2019 / Published: 14 October 2019
(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)
The micronutrients vitamins B9 and B12 act as methyl donors in the one-carbon metabolism involved in transmethylation reactions which critically influence epigenetic mechanisms and gene expression. Both vitamins are essential for proper development, and their deficiency during pregnancy has been associated with a wide range of disorders, including persisting growth retardation. Energy homeostasis and feeding are centrally regulated by the hypothalamus which integrates peripheral signals and acts through several orexigenic and anorexigenic mediators. We studied this regulating system in a rat model of methyl donor deficiency during gestation and lactation. At weaning, a predominance of the anorexigenic pathway was observed in deficient pups, with increased plasma peptide YY and increased hypothalamic pro-opiomelanocortin (POMC) mRNA, in line with abnormal leptin, ghrelin, and insulin secretion and/or signaling during critical periods of fetal and/or postnatal development of the hypothalamus. These results suggest that early methyl donor deficiency can affect the development and function of energy balance circuits, resulting in growth and weight deficits. Maternal administration of folic acid (3 mg/kg/day) during the perinatal period tended to rectify peripheral metabolic signaling and central neuropeptide and receptor expression, leading to reduced growth retardation. View Full-Text
Keywords: development; growth; hypothalamus; energy homeostasis; orexigenic and anorexigenic pathways; gestational deficiency; folate; vitamin B12; folate supplementation development; growth; hypothalamus; energy homeostasis; orexigenic and anorexigenic pathways; gestational deficiency; folate; vitamin B12; folate supplementation
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Saber Cherif, L.; Pourié, G.; Geoffroy, A.; Julien, A.; Helle, D.; Robert, A.; Umoret, R.; Guéant, J.-L.; Bossenmeyer-Pourié, C.; Daval, J.-L. Methyl Donor Deficiency during Gestation and Lactation in the Rat Affects the Expression of Neuropeptides and Related Receptors in the Hypothalamus. Int. J. Mol. Sci. 2019, 20, 5097.

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