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Metabolomics in Chronobiology: Metabolic Alterations by Sleep Loss and Circadian Function
1  Department of Systems Pharmacology and Translational Therapeutics, Perleman School of Medicine, University of Pennsylvania


Almost all organisms have a molecular clock which is responsive to external circadian cues, such as light:dark and temperature cycles. In turn, numerous rhythmic physiological processes are cyclical, such as energy balance, the sleep:wake cycle and cardio-metabolic function. Recently, time-dependent changes in metabolism and metabolic function have come to the fore via implication in various disease pathologies such as cancer and other metabolic diseases. Metabolite measurement through the circadian day requires reliable and quantitative methods to ensure temporal differences are accurately captured. Appropriate study design and data processing measures essential for detecting rhythmicity in metabolomics data are also required. Here a combination of analytical approaches based on nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography mass spectrometry (LC-MS) will be used in chronobiology measurements from both clinical and model systems. The tools included COLMeD, an LC-MS optimization strategy based on design of experiments methods, and NMR targeted profiling. Application of these tools to novel biological questions in the chronobiology area, such as the effects of sleep deprivation and interaction of the molecular clock with oncogene function will also be considered. Future developments in these technologies are anticipated vis-à-vis validating these early findings, given that metabolomics has only recently entered the ring with other systems biology assessments in chronobiology studies.

Keywords: chronobiology, sleep, circadian rhythms, nmr, lc-ms