Magnesium deficiency prevents high-fat-diet-induced obesity in mice

Aims/hypothesis: Hypomagnesaemia (blood Mg²⁺ <0.7 mmol/l) is a common phenomenon in individuals with type 2 diabetes. However, it remains unknown how a low blood Mg²⁺ concentration affects lipid and energy metabolism. Therefore, the importance of Mg²⁺ in obesity and type 2 diabetes has been largely neglected to date. This study aims to determine the effects of hypomagnesaemia on energy homeostasis and lipid metabolism.

Methods: Mice (n = 12/group) were fed either a low-fat diet (LFD) or a high-fat diet (HFD) (10% or 60% of total energy) in combination with a normal- or low-Mg²⁺ content (0.21% or 0.03% wt/wt) for 17 weeks. Metabolic cages were used to investigate food intake, energy expenditure and respiration. Blood and tissues were taken to study metabolic parameters and mRNA expression profiles, respectively.

Results: We show that low dietary Mg²⁺ intake ameliorates HFD-induced obesity in mice (47.00 ± 1.53 g vs 38.62 ± 1.51 g in mice given a normal Mg²⁺-HFD and low Mg²⁺-HFD, respectively, p < 0.05). Consequently, fasting serum glucose levels decreased and insulin sensitivity improved in low Mg²⁺-HFD-fed mice. Moreover, HFD-induced liver steatosis was absent in the low Mg²⁺ group. In hypomagnesaemic HFD-fed mice, mRNA expression of key lipolysis genes was increased in epididymal white adipose tissue (eWAT), corresponding to reduced lipid storage and high blood lipid levels. Low Mg²⁺-HFD-fed mice had increased brown adipose tissue (BAT) Ucp1 mRNA expression and a higher body temperature. No difference was observed in energy expenditure between the two HFD groups.

Conclusions/interpretation: Mg²⁺-deficiency abrogates HFD-induced obesity in mice through enhanced eWAT lipolysis and BAT activity.