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Interestingly, cardiomyocyte-restricted deletion of STIM1 (\n                    <jats:sup>cr<\/jats:sup>\n                    STIM1-KO) results in age-dependent endoplasmic reticulum stress, altered mitochondrial morphology, and dilated cardiomyopathy in mice. Here, we tested the hypothesis that STIM1 deficiency may also impact cardiac metabolism. Hearts isolated from 20-wk-old\n                    <jats:sup>cr<\/jats:sup>\n                    STIM1-KO mice exhibited a significant reduction in both oxidative and nonoxidative glucose utilization. Consistent with the reduction in glucose utilization, expression of glucose transporter 4 and AMP-activated protein kinase phosphorylation were all reduced, whereas pyruvate dehydrogenase kinase 4 and pyruvate dehydrogenase phosphorylation were increased, in\n                    <jats:sup>cr<\/jats:sup>\n                    STIM1-KO hearts. Despite similar rates of fatty acid oxidation in control and\n                    <jats:sup>cr<\/jats:sup>\n                    STIM1-KO hearts ex vivo,\n                    <jats:sup>cr<\/jats:sup>\n                    STIM1-KO hearts contained increased lipid\/triglyceride content as well as increased fatty acid-binding protein 4, fatty acid synthase, acyl-CoA thioesterase 1, hormone-sensitive lipase, and adipose triglyceride lipase expression compared with control hearts, suggestive of a possible imbalance between fatty acid uptake and oxidation. Insulin-mediated alterations in AKT phosphorylation were observed in\n                    <jats:sup>cr<\/jats:sup>\n                    STIM1-KO hearts, consistent with cardiac insulin resistance. Interestingly, we observed abnormal mitochondria and increased lipid accumulation in 12-wk\n                    <jats:sup>cr<\/jats:sup>\n                    STIM1-KO hearts, suggesting that these changes may initiate the subsequent metabolic dysfunction. These results demonstrate, for the first time, that cardiomyocyte STIM1 may play a key role in regulating cardiac metabolism.\n                  <\/jats:p>\n                  <jats:p>NEW &amp; NOTEWORTHY Little is known of the physiological role of stromal interaction molecule 1 (STIM1) in the heart. Here, we demonstrate, for the first time, that hearts lacking cardiomyocyte STIM1 exhibit dysregulation of both cardiac glucose and lipid metabolism. Consequently, these results suggest a potentially novel role for STIM1 in regulating cardiac metabolism.<\/jats:p>","DOI":"10.1152\/ajpheart.00544.2018","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T09:43:04Z","timestamp":1545385384000},"page":"H1014-H1026","source":"Crossref","is-referenced-by-count":25,"title":["Novel role of the ER\/SR Ca\n                    <sup>2+<\/sup>\n                    sensor STIM1 in the regulation of cardiac metabolism"],"prefix":"10.1152","volume":"316","author":[{"given":"Helen E.","family":"Collins","sequence":"first","affiliation":[{"name":"Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty M.","family":"Pat","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, 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