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To address this question, we noninvasively assessed rates of muscle ATP synthesis in hypophosphatemic mice by using\n                    <jats:italic>in vivo<\/jats:italic>\n                    saturation transfer [\n                    <jats:sup>31<\/jats:sup>\n                    P]\u2010magnetic resonance spectroscopy. By using this approach, we found that basal and insulin\u2010stimulated rates of muscle ATP synthetic flux (VATP) and plasma inorganic phosphate (Pi)were reduced by 50% in mice with diet\u2010induced hypophosphatemia as well as in sodium\u2010dependent P\n                    <jats:sub>i<\/jats:sub>\n                    transporter solute carrier family 34, member 1 (\n                    <jats:italic>NaPi2a<\/jats:italic>\n                    )\u2010knockout (\n                    <jats:italic>NaPi2a<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    ) mice compared with their wild\u2010type littermate controls. Rates of V\n                    <jats:sub>ATP<\/jats:sub>\n                    normalized in both hypophosphatemic groups after restoring plasma P\n                    <jats:sub>i<\/jats:sub>\n                    concentrations. Furthermore, V\n                    <jats:sub>ATP<\/jats:sub>\n                    was directly related to cellular and mitochondrial P\n                    <jats:sub>i<\/jats:sub>\n                    uptake in L6 and RC13 rodent myocytes and isolated muscle mitochondria. Similar findings were observed in a patient with chronic hypophosphatemia as a result of a mutation in SLC34A3 who had a 50% reduction in both serum P\n                    <jats:sub>i<\/jats:sub>\n                    content and muscle VATP. After oral P\n                    <jats:sub>i<\/jats:sub>\n                    repletion and normalization of serum P\n                    <jats:sub>i<\/jats:sub>\n                    levels, muscle V\n                    <jats:sub>ATP<\/jats:sub>\n                    completely normalized in the patient. Taken together, these data support the hypothesis that decreased muscle ATP synthesis, in part, may be caused by low blood P\n                    <jats:sub>i<\/jats:sub>\n                    concentrations, which may explain some aspects of muscle weakness observed in patients with hypophosphatemia.\u2014Pesta, D. H., Tsirigotis, D.N., Befroy, D.E., Caballero, D., Jurczak, M. J., Rahimi, Y., Cline, G.W., Dufour, S., Birkenfeld, A. L., Rothman, D.L., Carpenter, T. O., Insogna, K., Petersen, K. F., Bergwitz, C., Shulman, G. I. Hypophosphatemia promotes lower rates of muscle ATP synthesis. FASEB J. 30, 3378\u20133387 (2016).\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.201600473r","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T22:58:34Z","timestamp":1466722714000},"page":"3378-3387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Hypophosphatemia promotes lower rates of muscle ATP synthesis"],"prefix":"10.1096","volume":"30","author":[{"given":"Dominik H.","family":"Pesta","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios N.","family":"Tsirigotis","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas E.","family":"Befroy","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Engineering Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Caballero","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Jurczak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmeen","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary W.","family":"Cline","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Dufour","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas L.","family":"Birkenfeld","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas L.","family":"Rothman","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Engineering Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Insogna","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitt Falk","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Bergwitz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale 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