@article{10.1172/jci.insight.91722, author = {Noriko Uetani AND Serge Hardy AND Simon-Pierre Gravel AND Silke Kiessling AND Adam Pietrobon AND Nau Nau Wong AND Valérie Chénard AND Nicolas Cermakian AND Julie St-Pierre AND Michel L. Tremblay}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms}, year = {2017}, month = {7}, volume = {2}, url = {https://insight.jci.org/articles/view/91722}, abstract = {Magnesium (Mg2+) plays pleiotropic roles in cellular biology, and it is essentially required for all living organisms. Although previous studies demonstrated intracellular Mg2+ levels were regulated by the complex of phosphatase of regenerating liver 2 (PRL2) and Mg2+ transporter of cyclin M (CNNMs), physiological functions of PRL2 in whole animals remain unclear. Interestingly, Mg2+ was recently identified as a regulator of circadian rhythm–dependent metabolism; however, no mechanism was found to explain the clock-dependent Mg2+ oscillation. Herein, we report PRL2 as a missing link between sex and metabolism, as well as clock genes and daily cycles of Mg2+ 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–dependently 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 Mg2+ 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 Mg2+ levels, which accordingly controls energy metabolism status.}, number = {13}, doi = {10.1172/jci.insight.91722}, url = {https://doi.org/10.1172/jci.insight.91722}, }