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

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.

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.

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.

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