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Renal phospholipidosis and impaired magnesium handling in high‐fat‐diet–fed mice
Author(s) -
Kurstjens Steef,
Smeets Bart,
Overmars-Bos Caro,
Dijkman Henry B.,
Braanker Dirk J. W.,
Bel Thomas,
Bindels René J. M.,
Tack Cees J. J.,
Hoenderop Joost G. J.,
Baaij Jeroen H. F.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801778rr
Subject(s) - hypomagnesemia , endocrinology , medicine , distal convoluted tubule , kidney , insulin resistance , type 2 diabetes , hyperinsulinemia , renal function , biology , diabetes mellitus , chemistry , reabsorption , magnesium , organic chemistry
Hypomagnesemia (blood Mg 2+ 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 Mg 2+ 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 Mg 2+ , the HFD resulted in severe hypomagnesemia within 4 wk. Renal or intestinal Mg 2+ wasting was not observed after 16 wk on the diets. Despite the absence of urinary or fecal Mg 2+ 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 Mg 2+ 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). www.fasebj.org