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ABSTRACT: Circadian clocks maintain periodicity in internal cycles of behavior, physiology, and metabolism, enabling organisms to anticipate the 24-h rotation of the Earth. In mammals, circadian integration of metabolic systems optimizes energy harvesting and utilization across the light/dark cycle. Disruption of clock genes has recently been linked to sleep disorders and to the development of cardiometabolic disease. Conversely, aberrant nutrient signaling affects circadian rhythms of behavior. This chapter reviews the emerging relationship between the molecular clock and metabolic systems and examines evidence that circadian disruption exerts deleterious consequences on human health.
Handbook of experimental pharmacology 01/2013; 217:127-55.
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ABSTRACT: The circadian system synchronizes behavioral and physiologic processes with daily changes in the external light-dark cycle, optimizing energetic cycles with the rising and setting of the sun. Molecular clocks are organized hierarchically, with neural clocks orchestrating the daily switch between periods of feeding and fasting, and peripheral clocks generating 24h oscillations of energy storage and utilization. Recent studies indicate that clocks respond to nutrient signals and that a high-fat diet influences the period of locomotor activity under free-running conditions, a core property of the clock. A major goal is to identify the molecular basis for the reciprocal relation between metabolic and circadian pathways. Here the role of peptidergic hormones and macromolecules as nutrient signals integrating circadian and metabolic systems is highlighted.
Trends in Endocrinology and Metabolism 03/2012; 23(7):312-8. · 8.11 Impact Factor
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Darwin Jeyaraj,
Frank A J L Scheer,
Jürgen A Ripperger,
Saptarsi M Haldar,
Yuan Lu,
Domenick A Prosdocimo,
Sam J Eapen,
Betty L Eapen,
Yingjie Cui,
Ganapathi H Mahabeleshwar, [......],
Mark A Smith,
Gemma Casadesus,
Eric M Mintz,
Haipeng Sun,
Yibin Wang, Kathryn M Ramsey,
Joseph Bass,
Steven A Shea,
Urs Albrecht,
Mukesh K Jain
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ABSTRACT: Diurnal variation in nitrogen homeostasis is observed across phylogeny. But whether these are endogenous rhythms, and if so, molecular mechanisms that link nitrogen homeostasis to the circadian clock remain unknown. Here, we provide evidence that a clock-dependent peripheral oscillator, Krüppel-like factor 15 transcriptionally coordinates rhythmic expression of multiple enzymes involved in mammalian nitrogen homeostasis. In particular, Krüppel-like factor 15-deficient mice exhibit no discernable amino acid rhythm, and the rhythmicity of ammonia to urea detoxification is impaired. Of the external cues, feeding plays a dominant role in modulating Krüppel-like factor 15 rhythm and nitrogen homeostasis. Further, when all behavioral, environmental and dietary cues were controlled in humans, nitrogen homeostasis exhibited an endogenous circadian rhythmicity. Thus, in mammals, nitrogen homeostasis exhibits circadian rhythmicity, and is orchestrated by Krüppel-like factor 15.
Cell metabolism 03/2012; 15(3):311-23. · 17.35 Impact Factor
