Increased NEFA levels reduce blood Mg 2+ in hypertriacylglycerolaemic states via direct binding of NEFA to Mg 2 .

Autor:	Kurstjens S; Department of Physiology (286), Radboud Institute for Molecular Life Sciences, Radboud university medical center, P. O. Box 9101, 6500 HB, Nijmegen, the Netherlands., de Baaij JHF; Department of Physiology (286), Radboud Institute for Molecular Life Sciences, Radboud university medical center, P. O. Box 9101, 6500 HB, Nijmegen, the Netherlands.; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Overmars-Bos C; Department of Physiology (286), Radboud Institute for Molecular Life Sciences, Radboud university medical center, P. O. Box 9101, 6500 HB, Nijmegen, the Netherlands., van den Munckhof ICL; Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands., Garzero V; Department of Physiology (286), Radboud Institute for Molecular Life Sciences, Radboud university medical center, P. O. Box 9101, 6500 HB, Nijmegen, the Netherlands., de Vries MA; Department of Internal Medicine, Center for Diabetes and Vascular Medicine, Franciscus Gasthuis Rotterdam, Rotterdam, the Netherlands., Burggraaf B; Department of Internal Medicine, Center for Diabetes and Vascular Medicine, Franciscus Gasthuis Rotterdam, Rotterdam, the Netherlands., van Diepen JA; Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands., Riksen NP; Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands., Rutten JHW; Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands., Netea MG; Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.; Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany., Castro Cabezas M; Department of Internal Medicine, Center for Diabetes and Vascular Medicine, Franciscus Gasthuis Rotterdam, Rotterdam, the Netherlands., Bindels RJM; Department of Physiology (286), Radboud Institute for Molecular Life Sciences, Radboud university medical center, P. O. Box 9101, 6500 HB, Nijmegen, the Netherlands., Ashcroft FM; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Tack CJJ; Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands., Hoenderop JGJ; Department of Physiology (286), Radboud Institute for Molecular Life Sciences, Radboud university medical center, P. O. Box 9101, 6500 HB, Nijmegen, the Netherlands. joost.hoenderop@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	Diabetologia [Diabetologia] 2019 Feb; Vol. 62 (2), pp. 311-321. Date of Electronic Publication: 2018 Nov 13.
DOI:	10.1007/s00125-018-4771-3
Abstrakt:	Aims/hypothesis: The blood triacylglycerol level is one of the main determinants of blood Mg ²⁺ concentration in individuals with type 2 diabetes. Hypomagnesaemia (blood Mg ²⁺ 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 Mg ²⁺ concentrations. Methods: Using samples from 285 overweight individuals (BMI >27 kg/m ² ) 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 Mg ²⁺ 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 Mg ²⁺ , triacylglycerol and NEFA concentrations were measured using colourimetric assays. In vitro, NEFAs harvested from albumin were added in increasing concentrations to several Mg ²⁺ -containing solutions to study the direct interaction between Mg ²⁺ and NEFAs. Results: In the cohort of overweight individuals, serum Mg ²⁺ 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 Mg ²⁺ concentration both in mice (Δ plasma Mg ²⁺ -0.31 mmol/l at 4 h post oral gavage) and in healthy humans (Δ plasma Mg ²⁺ -0.07 mmol/l at 6 h post lipid intake). Further, in vitro experiments revealed that the decrease in plasma Mg ²⁺ may be explained by direct binding of Mg ²⁺ to NEFAs. Moreover, Mg ²⁺ was found to bind to albumin in a NEFA-dependent manner, evidenced by the fact that Mg ²⁺ did not bind to fatty-acid-free albumin. The NEFA-dependent reduction in the free Mg ²⁺ concentration was not affected by the presence of physiological concentrations of other cations. Conclusions/interpretation: This study shows that elevated NEFA and triacylglycerol levels directly reduce blood Mg ²⁺ levels, in part explaining the high prevalence of hypomagnesaemia in metabolic disorders. We show that blood NEFA level affects the free Mg ²⁺ concentration, and therefore, our data challenge how the fractional excretion of Mg ²⁺ is calculated and interpreted in the clinic.
Databáze:	MEDLINE
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