Magnesium Deficiency Alters Expression of Genes Critical for Muscle Magnesium Homeostasis and Physiology in Mice

Abstract

Chronic Mg²⁺ deficiency is the underlying cause of a broad range of health dysfunctions. As 25% of body Mg²⁺ is located in the skeletal muscle, Mg²⁺ transport and homeostasis systems (MgTHs) in the muscle are critical for whole-body Mg²⁺ homeostasis. In the present study, we assessed whether Mg²⁺ deficiency alters muscle fiber characteristics and major pathways regulating muscle physiology. C57BL/6J mice received either a control, mildly, or severely Mg²⁺-deficient diet (0.1%; 0.01%; and 0.003% Mg²⁺ wt/wt, respectively) for 14 days. Mg²⁺ deficiency slightly decreased body weight gain and muscle Mg²⁺ concentrations but was not associated with detectable variations in gastrocnemius muscle weight, fiber morphometry, and capillarization. Nonetheless, muscles exhibited decreased expression of several MgTHs (MagT1, CNNM2, CNNM4, and TRPM6). Moreover, TaqMan low-density array (TLDA) analyses further revealed that, before the emergence of major muscle dysfunctions, even a mild Mg²⁺ deficiency was sufficient to alter the expression of genes critical for muscle physiology, including energy metabolism, muscle regeneration, proteostasis, mitochondrial dynamics, and excitation-contraction coupling.

Keywords: magnesium; magnesium transporters; skeletal muscle; transcriptome.