Maternal Magnesium Deficiency in Mice Leads to Maternal Metabolic Dysfunction and Altered Lipid Metabolism with Fetal Growth Restriction

Madhu Gupta,Xiangying Xue,Prodyot K Chatterjee,Burton Rochelson,Christine N Metz,Neeraj Desai,Amanda Roman,Malvika H Solanki

doi:10.2119/molmed.2014.00137

Madhu Gupta, Xiangying Xue + Show 6 more

Open Access

https://doi.org/10.2119/molmed.2014.00137

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Abstract

Inadequate magnesium (Mg) intake is a widespread problem, with over 50% of women of reproductive age consuming less than the Recommended Dietary Allowance (RDA). Because pregnancy increases the requirement for Mg and the beneficial effects of magnesium sulfate for preeclampsia/eclampsia and fetal neuroprotection are well described, we examined the outcomes of Mg deficiency during pregnancy. Briefly, pregnant Swiss Webster mice were fed either control or Mg-deficient diets starting on gestational day (GD) 6 through euthanasia on GD17. Mg-deficient dams had significantly reduced weight gain and higher plasma adipokines, in the absence of inflammation. Livers of Mg-deficient dams had significantly higher saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) and lower polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) (P < 0.0001) and arachidonic acid (AA) (P < 0.0001). Mechanistically, Mg deficiency was accompanied by enhanced desaturase and elongase mRNA expression in maternal livers along with higher circulating insulin and glucose concentrations (P < 0.05) and increased mRNA expression of Srebf1 and Chrebp, regulators of fatty acid synthesis (P < 0.05). Fetal pups exposed to Mg deficiency were growth-restricted and exhibited reduced survival. Mg-deficient fetal livers showed lower MUFAs and higher PUFAs, with lower desaturase and elongase mRNA expression than controls. In addition, DHA concentrations were lower in Mg-deficient fetal brains (P < 0.05). These results indicate that Mg deficiency during pregnancy influences both maternal and fetal fatty acid metabolism, fetal growth and fetal survival, and support better understanding maternal Mg status before and during pregnancy.

Highlights

There is substantial evidence that nutritional status during pregnancy significantly affects maternal health and pregnancy outcomes
Mg is a required nutrient; it is essential for the activity of ATP and is a cofactor for over 300 biological enzymes, including those involved in glycolysis and lipid metabolism, as well as the synthesis of protein, RNA and DNA [3,4]
On the basis of the well-documented inadequate intakes of Mg before and during the reproductive years [1], the increased requirement for Mg during pregnancy, and the links between Mg deficiency and enhanced inflammation, aberrant lipid metabolism and insulin resistance [3,4,9,10,11,12], we examined the effects of Mg deficiency during pregnancy on maternal and fetal outcomes in mice

Summary

Introduction

There is substantial evidence that nutritional status during pregnancy significantly affects maternal health and pregnancy outcomes. Magnesium (Mg) deficiency is common and can be attributed to inadequate intake, impaired absorption, enhanced losses and/or increased biological requirements [1,2]. In addition to reduced consumption of Mg-containing foods, women are at risk for impaired Mg absorption and/or increased Mg losses because of obesity, diabetes, conditions of intestinal malabsorption, hormonal imbalances, the use of alcohol and/or drugs that compromise renal Mg handling (for example, nonsteroidal antiinflammatory agents, diuretics, antibiotics, excess calcium supplementation) and hyperemesis gravidarum, as well as excessive vomiting during pregnancy [3,4]. The daily requirement for Mg increases by approximately 30% to support the rapid growth of maternal, gestational and fetal

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