The Circadian Syndrome: is the Metabolic Syndrome and much more!

Zimmet, Paul; Alberti, K. G. M. M.; Stern, Naftali; Bilu, Carmel; El‐Osta, Assam; Einat, Haim; Kronfeld‐Schor, Noga

doi:10.1111/joim.12924

Cited by 239 publications

(222 citation statements)

References 111 publications

(201 reference statements)

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“…In the present study we present evidence showing that muscle contractions are a part of exercise that functions as a bona fide time cue for the skeletal muscle circadian clock. This finding could be of interest as exercise has the potential to work as a therapeutic to battle negative health outcomes linked to a lifestyle promoting circadian disruption as seen, for example, in shift workers (Morris et al 2016;Jørgensen et al 2017;Koshy et al 2019;Zimmet et al 2019). Our finding that exercise is a time cue for the skeletal muscle circadian clock in nocturnal rodents as well as in isolated muscle cells that are neither nocturnal nor diurnal, indicates that exercise could have similar effects in J Physiol 598.17 humans.…”

Section: Discussionmentioning

confidence: 75%

Time‐of‐day dependent effects of contractile activity on the phase of the skeletal muscle clock

Kemler

Wolff

Esser

2020

The Journal of Physiology

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Key points Disruptions in circadian rhythms across an organism are associated with negative health outcomes, such as cardiometabolic and neurodegenerative diseases. Exercise has been proposed as a time cue for the circadian clock in rodents and humans. In this study, we assessed the effect of a single bout of endurance exercise on the skeletal muscle clock in vivo and a bout of muscle contractions in vitro. Timing of exercise or contractions influences the directional response of the muscle clock phase in vivo and in vitro. Our findings demonstrate that muscle contractions, as a component of exercise, can directly modulate the expression of muscle clock components in a time‐of‐day dependent manner. Abstract Exercise has been proposed to be a zeitgeber for the muscle circadian clock mechanism. However, this is not well defined and it is unknown if exercise timing induces directional shifts of the muscle clock. Our purpose herein was to assess the effect of one bout of treadmill exercise on skeletal muscle clock phase changes. We subjected PERIOD2::LUCIFERASE mice (n = 30F) to one 60 min treadmill exercise bout at three times of day. Exercise at ZT5, 5 h after lights on, induced a phase advance (100.2 ± 25.8 min; P = 0.0002), whereas exercise at ZT11, 1 h before lights off, induced a phase delay (62.1 ± 21.1 min; P = 0.0003). Exercise at ZT17, middle of the dark phase, did not alter the muscle clock phase. Exercise induces diverse systemic changes so we developed an in vitro model system to examine the effects of contractile activity on muscle clock phase. Contractions applied at peak or trough Bmal1 expression induced significant phase delays (applied at peak: 27.2 ± 10.2 min; P = 0.0017; applied at trough: 64.6 ± 6.5 min, P < 0.0001). Contractions applied during the transition from peak to trough Bmal1 expression induced a phase advance (49.8 ± 23.1 min; P = 0.0051). Lastly, contractions at different times of day resulted in differential changes of core clock gene expression, demonstrating an exercise and clock interaction, providing insight into potential mechanisms of exercise‐induced phase shifts. These data demonstrate that muscle contractions, as part of exercise, are sufficient to shift the muscle circadian clock phase, likely through changes in core clock gene expression. Additionally, our findings that exercise induces directional muscle clock phase changes confirms that exercise is a bona fide environmental time cue for skeletal muscle.

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Section: Discussionmentioning

confidence: 75%

Time‐of‐day dependent effects of contractile activity on the phase of the skeletal muscle clock

Kemler

Wolff

Esser

2020

The Journal of Physiology

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“…including sleep disturbances, depression, steatohepatitis and cognitive impairment. In a recent publication Zimmet et al 39 proposed that circadian disruption may be an important underlying aetiological factor for the metabolic syndrome and suggest that it be renamed the 'circadian syndrome'.…”

Section: Circadian Rhythmmentioning

confidence: 99%

The metabolic syndrome – What is it and how should it be managed?

Nilsson

Tuomilehto

Rydén

2019

Eur J Prev Cardiolog

190

108

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A cluster of metabolic factors have been merged into an entity named the metabolic syndrome. Although the characteristics of this syndrome have varied over time the presently used definition was established in 2009. The presence of three abnormal findings out of five components qualifies a person for the metabolic syndrome: elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure and elevated fasting plasma glucose. Cut points have been defined for all components apart from waist circumference, for which national or regional values are used. The metabolic syndrome predicts cardiovascular disease and type 2 diabetes. This associated risk does not exceed its components whereof elevated blood pressure is the most frequent. A successful management should, however, address all factors involved. The management is always based on healthy lifestyle choices but has not infrequently to be supported by pharmacological treatment, especially blood pressure lowering drugs. The metabolic syndrome is a useful example of the importance of multiple targets for preventive interventions. To be successful management has to be individualized not the least when it comes to pharmacological therapy. Frail elderly people should not be over-treated. Knowledge transfer of how risk factors act should be accompanied by continuous trust building and motivation. In complex situations with a mix of biological risk factors, adverse social conditions and unhealthy lifestyle, everything cannot be changed at once. It is better to aim for small steps that are lasting than large, unsustainable steps with relapses to unhealthy behaviours. A person with the metabolic syndrome will always be afflicted by its components, which is the reason that management has to be sustained over a very long time. This review summarizes the knowledge on the metabolic syndrome and its management according to present state of the art.

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“…Circadian clock disruption, as observed in shift workers or people who frequently take transoceanic flights, has been related to metabolic disorders, increased incidence of cancer, sleep disturbances, and even neuropsychiatric diseases (Daut and Fonken, 2019;Zimmet et al, 2019). Interestingly, the intestinal microflora are involved in all of the abovementioned conditions.…”

Section: Gut Microbiota-brain Axis and The Potential Influence Of Micmentioning

confidence: 99%

The Circadian Clock as an Essential Molecular Link Between Host Physiology and Microorganisms

Murakami

Tognini

2020

Front. Cell. Infect. Microbiol.

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Advances in high-throughput sequencing technologies in the past decade has led to a tremendous growth in knowledge about the role played by microorganisms on our body health. Trillions of microbes live in close symbiosis with their host, and have impacts on various aspects of host physiology as well as predisposition to disease. This is a consequence of the direct interaction between host cells and microbes or their signaling molecules, such as metabolites, which can reach and exert their effects in distal tissues. Among the essential factors modulating the human body's ecosystem of symbionts, the circadian clock might be one of the key regulators. The endogenous clock is a highly conserved timekeeper able to align organismal physiology to the daily cycle, thus maximizing survival and fitness. Circadian rhythms coordinate whole-body biological processes synchronizing cellular biochemical reactions, tissue function and finally controlling systemic homeostasis. Intriguingly, growing body of evidence has demonstrated that the host circadian cycle governs the structure of the gut microbiota community and its diurnal rhythmicity, whereas the microbes contribute to maintenance of clock function. In this review, we will give an overview of the multisystem aspects of microbiome-host interactions in the context of circadian rhythmicity. In particular, the effect of the interaction clock-microbial communities on immune system function and metabolic homeostasis will be discussed. Finally, the possible implication of daily rhythm on the gut-microbiome-brain axis will be analyzed, focusing on the reciprocal effects of clock disruption and microbiota alterations on brain function and behavior.

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The Circadian Syndrome: is the Metabolic Syndrome and much more!

Cited by 239 publications

References 111 publications

Time‐of‐day dependent effects of contractile activity on the phase of the skeletal muscle clock

Time‐of‐day dependent effects of contractile activity on the phase of the skeletal muscle clock

The metabolic syndrome – What is it and how should it be managed?

The Circadian Clock as an Essential Molecular Link Between Host Physiology and Microorganisms

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