Time-restricted feeding and the realignment of biological rhythms: translational opportunities and challenges
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REVIEW
Open Access
Time-restricted feeding and the realignment of biological rhythms: translational opportunities and challenges Jag Sunderram1, Stavroula Sofou2,3, Kubra Kamisoglu3, Vassiliki Karantza4 and Ioannis P Androulakis2,3*
Abstract It has been argued that circadian dysregulation is not only a critical inducer and promoter of adverse health effects, exacerbating symptom burden, but also hampers recovery. Therefore understanding the health-promoting roles of regulating (i.e., restoring) circadian rhythms, thus suppressing harmful effects of circadian dysregulation, would likely improve treatment. At a critical care setting it has been argued that studies are warranted to determine whether there is any use in restoring circadian rhythms in critically ill patients, what therapeutic goals should be targeted, and how these could be achieved. Particularly interesting are interventional approaches aiming at optimizing the time of feeding in relation to individualized day–night cycles for patients receiving enteral nutrition, in an attempt to re-establish circadian patterns of molecular expression. In this short review we wish to explore the idea of transiently imposing (appropriate, but yet to be determined) circadian rhythmicity via regulation of food intake as a means of exploring rhythm-setting properties of metabolic cues in the context of improving immune response. We highlight some of the key elements associated with his complex question particularly as they relate to: a) stress and rhythmic variability; and b) metabolic entrainment of peripheral tissues as a possible intervention strategy through time-restricted feeding. Finally, we discuss the challenges and opportunities for translating these ideas to the bedside.
Introduction Biological rhythms are major determinants of behavioural outcome [1,2] and are controlled by a tightly regulated network of genes and proteins entrained by external signals (light and food). The suprachiasmatic nucleus (SCN) is the fundamental, central, regulator of circadian rhythmicity (biological rhythms of, roughly, 24 h period) and is considered the master clock designed to align, and coordinate the independent, self-sustained, peripheral oscillators (a.k.a. peripheral clocks) found in every cell, tissue and organ [3-6]. In that respect, understanding the mechanisms by which the various pacemakers interact to coordinate functions becomes a critical question [7]. Despite the fact that all peripheral clocks effectively utilize the same time-keeping machinery [8-11] (Figure 1) each peripheral entity is impacted by unique stimuli capable of * Correspondence: [email protected] 2 Biomedical Engineering Department, Rutgers University, Piscataway, NJ 08854, USA 3 Chemical & Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854, USA Full list of author information is available at the end of the article
setting clock rhythmicity locally, directly or indirectly. As such, core physiological functions are strongly impacted by the appropriate alignment of pe
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