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We present a bioluminescent reporter based on copper-dependent uncaging of a\n                    <jats:sc>d<\/jats:sc>\n                    -luciferin substrate for selective, sensitive, and tissue-specific longitudinal imaging of labile copper pools in animal model systems. Application of this technology to monitor a diet-induced mouse model of nonalcoholic fatty liver disease, a disorder affecting\n                    <jats:italic>ca<\/jats:italic>\n                    . 100 million Americans, reveals hepatic copper deficiency and altered expression levels of copper homeostatic proteins that accompany glucose intolerance and weight gain. 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