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In patients with T2D, reduced blood Mg\n                    <jats:sup>2+<\/jats:sup>\n                    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\u2010fat\u2010diet (HFD)\u2010fed mice. In mice fed a low dietary Mg\n                    <jats:sup>2+<\/jats:sup>\n                    , the HFD resulted in severe hypomagnesemia within 4 wk. Renal or intestinal Mg\n                    <jats:sup>2+<\/jats:sup>\n                    wasting was not observed after 16 wk on the diets. Despite the absence of urinary or fecal Mg\n                    <jats:sup>2+<\/jats:sup>\n                    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)\u2010specific genes was down\u2010regulated by the LowMg\u2010HFD, indicating atrophy of the DCT. The low dietary Mg\n                    <jats:sup>2+<\/jats:sup>\n                    resulted in severe HFD\u2010induced proximal tubule phospholipidosis, which was absent in mice on a NormalMg\u2010HFD. This was accompanied by albuminuria, moderate renal damage, and alterations in renal energy metabolism, including enhanced gluconeo\u2010genesis and cholesterol synthesis. In conclusion, this study shows that hypomagnesemia is a consequence of diet\u2010induced 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.\u2014Kurstjens, S., Smeets, B., Overmars\u2010Bos, 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\u2010fat\u2010diet\u2013fed mice. FASEB J. 33, 7192\u20137201 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801778rr","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T14:16:02Z","timestamp":1552054562000},"page":"7192-7201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Renal phospholipidosis and impaired magnesium handling in high\u2010fat\u2010diet\u2013fed mice"],"prefix":"10.1096","volume":"33","author":[{"given":"Steef","family":"Kurstjens","sequence":"first","affiliation":[{"name":"Department of Physiology Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Smeets","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caro","family":"Overmars-Bos","sequence":"additional","affiliation":[{"name":"Department of Physiology Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry B.","family":"Dijkman","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk J. 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