title: Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver.
abstract: Diagnosis and therapeutic interventions in pathological conditions rely upon clinical monitoring of key metabolites in the serum. Recent studies show that a wide range of metabolic pathways are controlled by circadian rhythms whose oscillation is affected by nutritional challenges, underscoring the importance of assessing a temporal window for clinical testing and thereby questioning the accuracy of the reading of critical pathological markers in circulation. We have been interested in studying the communication between peripheral tissues under metabolic homeostasis perturbation. Here we present a comparative circadian metabolomic analysis on serum and liver in mice under high fat diet. Our data reveal that the nutritional challenge induces a loss of serum metabolite rhythmicity compared with liver, indicating a circadian misalignment between the tissues analyzed. Importantly, our results show that the levels of serum metabolites do not reflect the circadian liver metabolic signature or the effect of nutritional challenge. This notion reveals the possibility that misleading reads of metabolites in circulation may result in misdiagnosis and improper treatments. Our findings also demonstrate a tissue-specific and time-dependent disruption of metabolic homeostasis in response to altered nutrition.
authors.affiliation: From the Center for Epigenetics and Metabolism, U904 INSERM, and the Department of Biological Chemistry, University of California, Irvine, California 92697-4625 and.
authors.forename: Serena
authors.initials: S
authors.lastname: Abbondante
authors.affiliation: From the Center for Epigenetics and Metabolism, U904 INSERM, and the Department of Biological Chemistry, University of California, Irvine, California 92697-4625 and.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Eckel-Mahan
authors.affiliation: the Department of Biological Chemistry, University of California, Irvine, California 92697-4625 and the Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, California 92697-3435.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Ceglia
authors.affiliation: the Department of Biological Chemistry, University of California, Irvine, California 92697-4625 and the Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, California 92697-3435.
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
authors.affiliation: From the Center for Epigenetics and Metabolism, U904 INSERM, and the Department of Biological Chemistry, University of California, Irvine, California 92697-4625 and psc@uci.edu.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002940:Circadian Rhythm; D004041:Dietary Fats / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D055432:Metabolomics; D051379:Mice
chemical_list: D001798:Blood Proteins; D004041:Dietary Fats
keywords: circadian rhythm; liver; metabolism; metabolomics; serum