Magnesium stable isotope composition, but not concentration, responds to obesity and early insulin-resistant conditions in minipig

Abstract

Hypomagnesemia is frequently associated with type 2 diabetes and generally correlates with unfavorable disease progression, but the magnesium status in pre-diabetic conditions remains unclear. Here, the magnesium metabolism is scrutinized in a minipig model of obesity and insulin resistance by measuring variations of the metallome-the set of inorganic elements-and the magnesium stable isotope composition in six organs of lean and obese minipigs raised on normal and Western-type diet, respectively. We found that metallomic variations are most generally insensitive to lean or obese phenotypes. The magnesium stable isotope composition of plasma, liver, kidney, and heart in lean minipigs are significantly heavier than in obese minipigs. For both lean and obese minipigs, the magnesium isotope composition of plasma and liver were negatively correlated to clinical phenotypes and plasma lipoproteins concentration as well as positively correlated to hyperinsulinemic-euglycemic clamp output. Because the magnesium isotope composition was not associated to insulin secretion, our results suggest that it is rather sensitive to whole body insulin sensitivity, opening perspectives to better comprehend the onset of insulin-resistant diabetic conditions.

Figure 1

Distribution of the Mg isotope composition in organs on lean and insulin-resistant/obese (IR-O) minipigs. (A) δ²⁶Mg value in organs, diet and water. (B) diet-corrected δ²⁶Mg value (∆²⁶Mg_D) in organs. Results of Wilcoxon test P value between lean and IR-O minipigs are given. Error bars are two standards deviations of the mean. ***P < 0.001, **P < 0.01, *P < 0.05, NS P > 0.05.

Figure 2

Heatmap of Spearman Rho coefficients of correlations between ∆²⁶Mg_D values and phenotypes. Adjusted P value for multiple testing with the Benjamini & Hochberg correction are given: ***Adj.P < 0.001, **Adj.P < 0.01, *Adj.P < 0.05, ‘Adj.P < 0.1.

Figure 3

Scatterplots of selected significant correlations discussed in the text. Spearman Rho coefficients and associated P values are given ***P < 0.001, **P < 0.01, *P < 0.05.