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

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.