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

Kurstjens, Steef; Diepen, Janna A. van; Bos, Caro; Alkema, Wynand; Bindels, René J. M.; Ashcroft, Frances M.; Tack, Cees J.; Hoenderop, Joost G. J.; Baaij, Jeroen H. F. de

doi:10.1007/s00125-018-4680-5

Cited by 17 publications

(13 citation statements)

References 48 publications

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“…These findings were attributed to lower rates of oxidative stress and apoptosis [12]. However, Kurstjens et al showed that a lower dietary magnesium intake ameliorated high-fat diet-induced obesity in mice [13]. Thus, more studies are necessary to clarify the relationship between dietary magnesium intake and LTL.…”

Section: Introductionmentioning

confidence: 99%

Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α

Liu

et al. 2020

Mediators of Inflammation

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Objectives. In this study, we assessed the effects of dietary magnesium on leukocyte telomere length (LTL). Designs. The current cross-sectional analysis was based on data collected within a type 2 diabetes project. Settings. Dietary magnesium intake is associated with peripheral blood leukocyte telomere length (LTL). However, few epidemiological studies have evaluated the effects of magnesium on LTL in the clinical setting. Participants. This cross-sectional analysis included 467 participants (34.8% men). Measurements. Serum blood lipid profile, HbA1c, oxidative stress, and proinflammatory mediator levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Regression models and simple regulatory models were used for data analysis. Results. There was an inverse relationship between dietary magnesium and LTL (P<0.001), with a between-extreme-quarter difference of -0.55. Conversely, there was a positive relationship between dietary magnesium and serum tumor necrosis factor (TNF) α, with an interquarter difference of 3.79 pmol/mL (P for trend=0.006). Multivariate regression analysis revealed that the odds ratios (ORs) for shorter LTL and higher serum TNFα increased with magnesium intake, and the ORs of the differences between extreme quartiles were 2.60 (95% confidence interval (CI): 1.31–5.36; P=0.003) and 1.98 (95% CI: 1.09–3.59; P=0.008). There was a direct negative effect of dietary magnesium intake on LTL (B=−0.002; P=0.001), which appeared to be indirectly influenced by TNFα (-0.002 to -0.0005). Conclusions. Dietary magnesium intake may be a critical component of the cellular aging process, and its effect could be partly mediated by TNFα.

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Section: Introductionmentioning

confidence: 99%

Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α

Liu

et al. 2020

Mediators of Inflammation

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“…To investigate the effect of diet-induced obesity and insulin resistance on Mg 2+ homeostasis, mice were fed a LFD or an HFD combined with a normal or low dietary Mg 2+ content. Data on the metabolic parameters, water and food intake, and urinary volume of these mice have been published previously (20). Both low Mg 2+ diet groups showed decreased serum Mg 2+ levels after 17 wk on the diet (Fig.…”

Section: Hfd Feeding Induces Severe Hypomagnesemiamentioning

confidence: 78%

“…This study was approved by the Animal Ethics Board of the Radboud University Nijmegen (RU DEC 2015-0073) and by the Dutch Central Commission for Animal Experiments (AVD103002015239). Fourty-eight male C57BL6/J mice (Charles River Laboratories, Wilmington, MA, USA) were allocated randomly into 4 groups of mice (n = 12/group) (20). Mice, obtained at 9-10 wk of age, were acclimatized for 2 wk in a temperature-and light-controlled room, 6 mice/cage (Eurostandard Type III).…”

Section: Mouse Studymentioning

confidence: 99%

Renal phospholipidosis and impaired magnesium handling in high‐fat‐diet–fed mice

et al. 2019

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Hypomagnesemia (blood Mg2+ concentration <0.7 mM) is a common electrolyte disorder in patients with type 2 diabetes (T2D), but the etiology remains largely unknown. In patients with T2D, reduced blood Mg2+ levels are associated with an increased decline in renal function, independent of glycemic control and hypertension. To study the underlying mechanism of this phenomenon, we investigated the renal effects of hypomagnesemia in high‐fat‐diet (HFD)‐fed mice. In mice fed a low dietary Mg2+, the HFD resulted in severe hypomagnesemia within 4 wk. Renal or intestinal Mg2+ wasting was not observed after 16 wk on the diets. Despite the absence of urinary or fecal Mg2+ loss, the HFD induced a reduction in the mRNA expression transient receptor potential melastatin type 6 in both the kidney and colon. mRNA expression of distal convoluted tubule (DCT)‐specific genes was down‐regulated by the LowMg‐HFD, indicating atrophy of the DCT. The low dietary Mg2+ resulted in severe HFD‐induced proximal tubule phospholipidosis, which was absent in mice on a NormalMg‐HFD. This was accompanied by albuminuria, moderate renal damage, and alterations in renal energy metabolism, including enhanced gluconeo‐genesis and cholesterol synthesis. In conclusion, this study shows that hypomagnesemia is a consequence of diet‐induced obesity and insulin resistance. Moreover, hypomagnesemia induces major structural changes in the diabetic kidney, including proximal tubular phospholipidosis, providing a novel mechanism for the increased renal decline in patients with hypomagnesemic T2D.—Kurstjens, S., Smeets, B., Overmars‐Bos, C., Dijkman, H. B., den Braanker, D. J. W., de Bel, T., Bindels, R. J. M., Tack, C. J. J., Hoenderop, J. G. J., de Baaij, J. H. F. Renal phospholipidosis and impaired magnesium handling in high‐fat‐diet–fed mice. FASEB J. 33, 7192–7201 (2019). http://www.fasebj.org

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“…Severe hypomagnesaemia in animals leads to increased blood triacylglycerol levels, possibly by disrupting the function of the enzyme lecithin-cholesterol acyltransferase or by activating lipolysis in adipose tissue [25, 26]. However, whether triacylglycerols can affect Mg 2+ homeostasis has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

“…In metabolic diseases, high blood triacylglycerol concentrations are associated with a lower blood Mg 2+ concentration, but the directionality of this correlation remains unclear [ 1 , 23 , 24 ]. Severe hypomagnesaemia in animals leads to increased blood triacylglycerol levels, possibly by disrupting the function of the enzyme lecithin-cholesterol acyltransferase or by activating lipolysis in adipose tissue [ 25 , 26 ]. However, whether triacylglycerols can affect Mg 2+ homeostasis has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Increased NEFA levels reduce blood Mg2+ in hypertriacylglycerolaemic states via direct binding of NEFA to Mg2+

et al. 2018

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Aims/hypothesisThe blood triacylglycerol level is one of the main determinants of blood Mg2+ concentration in individuals with type 2 diabetes. Hypomagnesaemia (blood Mg2+ concentration <0.7 mmol/l) has serious consequences as it increases the risk of developing type 2 diabetes and accelerates progression of the disease. This study aimed to determine the mechanism by which triacylglycerol levels affect blood Mg2+ concentrations.MethodsUsing samples from 285 overweight individuals (BMI >27 kg/m2) who participated in the 300-Obesity study (an observational cross-sectional cohort study, as part of the Human Functional Genetics Projects), we investigated the association between serum Mg2+ with laboratory variables, including an extensive lipid profile. In a separate set of studies, hyperlipidaemia was induced in mice and in healthy humans via an oral lipid load, and blood Mg2+, triacylglycerol and NEFA concentrations were measured using colourimetric assays. In vitro, NEFAs harvested from albumin were added in increasing concentrations to several Mg2+-containing solutions to study the direct interaction between Mg2+ and NEFAs.ResultsIn the cohort of overweight individuals, serum Mg2+ levels were inversely correlated with triacylglycerols incorporated in large VLDL particles (r = −0.159, p ≤ 0.01). After lipid loading, we observed a postprandial increase in plasma triacylglycerol and NEFA levels and a reciprocal reduction in blood Mg2+ concentration both in mice (Δ plasma Mg2+ −0.31 mmol/l at 4 h post oral gavage) and in healthy humans (Δ plasma Mg2+ −0.07 mmol/l at 6 h post lipid intake). Further, in vitro experiments revealed that the decrease in plasma Mg2+ may be explained by direct binding of Mg2+ to NEFAs. Moreover, Mg2+ was found to bind to albumin in a NEFA-dependent manner, evidenced by the fact that Mg2+ did not bind to fatty-acid-free albumin. The NEFA-dependent reduction in the free Mg2+ concentration was not affected by the presence of physiological concentrations of other cations.Conclusions/interpretationThis study shows that elevated NEFA and triacylglycerol levels directly reduce blood Mg2+ levels, in part explaining the high prevalence of hypomagnesaemia in metabolic disorders. We show that blood NEFA level affects the free Mg2+ concentration, and therefore, our data challenge how the fractional excretion of Mg2+ is calculated and interpreted in the clinic.Electronic supplementary materialThe online version of this article (10.1007/s00125-018-4771-3) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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

Cited by 17 publications

References 48 publications

Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α

Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α

Renal phospholipidosis and impaired magnesium handling in high‐fat‐diet–fed mice

Increased NEFA levels reduce blood Mg2+ in hypertriacylglycerolaemic states via direct binding of NEFA to Mg2+

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