Expression of magnesium responsive genes in murine metabolic liver diseases

Introduction:

Type 2 diabetes (T2D) and non-alcoholic fatty liver diseases (NAFLD) are frequently associated with hypomagnesaemia, abnormal mitochondrial function and endoplasmic reticulum (ER) stress. According to recent studies, gene variants encoding the solute carrier family 41 members (SLC41A), which regulate Mg2+ transport, associate with T2D risk. To this end, this study aimed at analyzing the expression of magnesium-responsive genes in livers of insulin sensitive mice and NAFLD models.

Methods:

A total of 15 8-weeks old mice were randomly allocated to three dietary interventions: standard-(STD), high fat-(HFD) or methionine-choline deficient-(MCD) diet for the following 8 weeks. Expression of selected MRGs was performed in the livers by using quantitative real-time polymerase chain reaction, while expression of ER stress-associated and oxidative phosphorylation (OXPHOS) proteins was analyzed with Western blotting.

Results:

At baseline, body weight and glycemia were comparable in all groups. After 8 weeks, both decreased in MCD (p < 0.0001), while body weight increased only in HFD (p < 0.001). The mRNA expression of SLC41A2 and SLC41A3 was increased in HFD (p < 0.01) and MCD (p < 0.05). Expression of 78KDa-glucose regulated protein (GRP78) was highest in MCD (p < 0.01), while that of OXPHOS tended to be higher in HFD (p < 0.1)

Conclusions:

Differential expression of SLC41 members in different models of metabolic liver diseases suggests the operation of specific compensatory mechanisms by which hepatocytes release Mg2+ from mitochondrial and ER/Golgi compartment.