{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:30:11Z","timestamp":1791261011171,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,6]]},"abstract":"<jats:p>\n                    Magnesium (Mg\n                    <jats:sup>2+<\/jats:sup>\n                    ) plays pleiotropic roles in cellular biology, and it is essentially required for all living organisms. Although previous studies demonstrated intracellular Mg\n                    <jats:sup>2+<\/jats:sup>\n                    levels were regulated by the complex of phosphatase of regenerating liver 2 (PRL2) and Mg\n                    <jats:sup>2+<\/jats:sup>\n                    transporter of cyclin M (CNNMs), physiological functions of PRL2 in whole animals remain unclear. Interestingly, Mg\n                    <jats:sup>2+<\/jats:sup>\n                    was recently identified as a regulator of circadian rhythm\u2013dependent metabolism; however, no mechanism was found to explain the clock-dependent Mg\n                    <jats:sup>2+<\/jats:sup>\n                    oscillation. Herein, we report PRL2 as a missing link between sex and metabolism, as well as clock genes and daily cycles of Mg\n                    <jats:sup>2+<\/jats:sup>\n                    fluxes. Our results unveil that PRL2-null animals displayed sex-dependent alterations in body composition, and expression of PRLs and CNNMs were sex- and circadian time\u2013dependently regulated in brown adipose tissues. Consistently, PRL2-KO mice showed sex-dependent alterations in thermogenesis and in circadian energy metabolism. These physiological changes were associated with an increased rate of uncoupled respiration with lower intracellular Mg\n                    <jats:sup>2+<\/jats:sup>\n                    in PRL2-KO cells. Moreover, PRL2 deficiency causes inhibition of the ATP citrate lyase axis, which is involved in fatty acid synthesis. Overall, our findings support that sex- and circadian-dependent PRL2 expression alter intracellular Mg\n                    <jats:sup>2+<\/jats:sup>\n                    levels, which accordingly controls energy metabolism status.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.91722","type":"journal-article","created":{"date-parts":[[2017,7,5]],"date-time":"2017-07-05T11:26:07Z","timestamp":1499253967000},"source":"Crossref","is-referenced-by-count":25,"title":["PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms"],"prefix":"10.1172","volume":"2","author":[{"given":"Noriko","family":"Uetani","sequence":"first","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Research Centre,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Hardy","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Research 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