Hormonal regulation of core clock gene expression in skeletal muscle following acute aerobic exercise

2019 ◽  
Vol 508 (3) ◽  
pp. 871-876 ◽  
Author(s):  
Patrick G. Saracino ◽  
Michael L. Rossetti ◽  
Jennifer L. Steiner ◽  
Bradley S. Gordon
Author(s):  
Denise Kemler ◽  
Christopher A. Wolff ◽  
Karyn A. Esser

ABSTRACTExercise 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-minute treadmill exercise bout at three times of day. Exercise at ZT5, 5h after lights on, induced a phase advance (1.4±0.53h; p=0.038), whereas exercise at ZT11, 1h before lights off, induced a phase delay (−0.95±0.43h; p=0.0315). Exercise at ZT17, middle of the dark phase, did not alter muscle clock phase. Exercise induces diverse systemic changes so we developed an in-vitro model system to examine effects of contractile activity on muscle clock phase. Contractions applied at peak or trough Bmal1 expression induced significant phase delays (applied at peak: 1.3±0.02h; p=0.0425; applied at trough: 1.8±0.02h, p=0.0074). Contractions applied during the transition from peak to trough Bmal1 expression induced a phase advance (1.8±0.03h; p=0.0265). 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 exercise-induced phase shifts. These data demonstrate that muscle contractions, as part of exercise, are sufficient to shift muscle circadian clock phase, likely through changes in core-clock gene expression. Additionally, our findings that exercise induces directional muscle clock phase changes confirms exercise is a bone fide environmental time cue for skeletal muscle.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Leonidas S. Lundell ◽  
Evelyn B. Parr ◽  
Brooke L. Devlin ◽  
Lars R. Ingerslev ◽  
Ali Altıntaş ◽  
...  

Abstract Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction. To elucidate mechanisms underpinning the effects of short-term TRF, we investigated skeletal muscle and serum metabolic and transcriptomic profiles from 11 men with overweight/obesity after TRF (8 h day−1) and extended feeding (EXF, 15 h day−1) in a randomised cross-over design (trial registration: ACTRN12617000165381). Here we show that muscle core clock gene expression was similar after both interventions. TRF increases the amplitude of oscillating muscle transcripts, but not muscle or serum metabolites. In muscle, TRF induces rhythmicity of several amino acid transporter genes and metabolites. In serum, lipids are the largest class of periodic metabolites, while the majority of phase-shifted metabolites are amino acid related. In conclusion, short-term TRF in overweight men affects the rhythmicity of serum and muscle metabolites and regulates the rhythmicity of genes controlling amino acid transport, without perturbing core clock gene expression.


2010 ◽  
Vol 299 (3) ◽  
pp. R751-R761 ◽  
Author(s):  
Carrie E. Mahoney ◽  
Daniel Brewer ◽  
Mary K. Costello ◽  
Judy McKinley Brewer ◽  
Eric L. Bittman

To evaluate the contribution of neural pathways to the determination of the circadian oscillator phase in peripheral organs, we assessed lateralization of clock gene expression in Syrian hamsters induced to split rhythms of locomotor activity by exposure to constant light. We measured the ratio of haPer1, haPer2, and haBmal1 mRNA on the high vs. low (H/L) side at 3-h intervals prior to the predicted activity onset (pAO). We also calculated expression on the sides ipsilateral vs. contralateral (I/C) to the side of the suprachiasmatic nucleus (SCN) expressing higher haPer1. The extent of asymmetry in split hamsters varied between specific genes, phases, and organs. Although the magnitude of asymmetry in peripheral organs was never as great as that in the SCN, we observed significantly greater lateralization of clock gene expression in the adrenal medulla and cortex, lung, and skeletal muscle, but not in liver or kidney, of split hamsters than of unsplit controls. We observed fivefold lateralization of expression of the clock-controlled gene, albumin site D-element binding protein ( Dbp), in skeletal muscle (H/L: 10.7 ± 3.7 at 3 h vs. 2.2 ± 0.3 at 0 h pAO; P = 0.03). Furthermore, tyrosine hydroxylase expression was asymmetrical in the adrenal medulla of split (H/L: 1.9 ± 0.5 at 0 h) vs. unsplit hamsters (1.2 ± 0.04; P < 0.05). Consistent with a model of neurally controlled gene expression, we found significant correlations between the phase angle between morning and evening components (ψme) and the level of asymmetry (H/L or I/C). Our results indicate that neural pathways contribute to, but cannot completely account for, SCN regulation of the phase of peripheral oscillators.


2020 ◽  
Vol 318 (1) ◽  
pp. E1-E10 ◽  
Author(s):  
Laura Sardon Puig ◽  
Nicolas J. Pillon ◽  
Erik Näslund ◽  
Anna Krook ◽  
Juleen R. Zierath

The molecular circadian clock plays a role in metabolic homeostasis. We tested the hypothesis obesity and systemic factors associated with insulin resistance affect skeletal muscle clock gene expression. We determined clock gene expression in skeletal muscle of obese women ( n = 5) and men ( n = 18) before and 6 mo after Roux-en-Y gastric bypass (RYGB) surgery and normal-weight controls (women n = 6, men n = 8). Skeletal muscle clock gene expression was affected by obesity and weight loss. CRY1 mRNA ( P = 0.05) was increased and DBP mRNA ( P < 0.05) was decreased in obese vs. normal weight women and restored to control levels after RYGB-induced weight loss. CLOCK, CRY1, CRY2, and DBP mRNA ( P < 0.05) was decreased in obese men compared with normal weight men. Expression of all other clock genes was unaltered by obesity or weight loss in both cohorts. We correlated clock gene expression with clinical characteristics of the participants. Among the genes studied, DBP and PER3 expression was inversely correlated with plasma lipids in both cohorts. Circadian time-course studies revealed that core clock genes oscillate over time ( P < 0.05), with BMAL1, CIART, CRY2, DBP, PER1, and PER3 expression profiles altered by palmitate treatment. In conclusion, skeletal muscle clock gene expression and function is altered by obesity, coincident with changes in plasma lipid levels. Palmitate exposure disrupts clock gene expression in myotubes, indicating that dyslipidemia directly alters the circadian program. Strategies to reduce lipid overload and prevent elevations in nonesterified fatty acid and cholesterol levels may sustain circadian clock signals in skeletal muscle.


Diabetologia ◽  
2017 ◽  
Vol 60 (10) ◽  
pp. 2011-2020 ◽  
Author(s):  
Cécile Jacovetti ◽  
Adriana Rodriguez-Trejo ◽  
Claudiane Guay ◽  
Jonathan Sobel ◽  
Sonia Gattesco ◽  
...  

2007 ◽  
Vol 293 (4) ◽  
pp. R1528-R1537 ◽  
Author(s):  
David J. Kennaway ◽  
Julie A. Owens ◽  
Athena Voultsios ◽  
Michael J. Boden ◽  
Tamara J. Varcoe

The role of peripheral vs. central circadian rhythms and Clock in the maintenance of metabolic homeostasis and with aging was examined by using ClockΔ19 +MEL mice. These have preserved suprachiasmatic nucleus and pineal gland rhythmicity but arrhythmic Clock gene expression in the liver and skeletal muscle. ClockΔ19 +MEL mice showed fasting hypoglycemia in young-adult males, fasting hyperglycemia in older females, and substantially impaired glucose tolerance overall. ClockΔ19 +MEL mice had substantially reduced plasma insulin and plasma insulin/glucose nocturnally in males and during a glucose tolerance test in females, suggesting impaired insulin secretion. ClockΔ19 +MEL mice had reduced hepatic expression and loss of rhythmicity of gck, pfkfb3, and pepck mRNA, which is likely to impair glycolysis and gluconeogenesis. ClockΔ19 +MEL mice also had reduced glut4 mRNA in skeletal muscle, and this may contribute to poor glucose tolerance. Whole body insulin tolerance was enhanced in ClockΔ19 +MEL mice, however, suggesting enhanced insulin sensitivity. These responses occurred although the ClockΔ19 mutation did not cause obesity and reduced plasma free fatty acids while increasing plasma adiponectin. These studies on clock-gene disruption in peripheral tissues and metabolic homeostasis provide compelling evidence of a relationship between circadian rhythms and the glucose/insulin and adipoinsular axes. It is, however, premature to declare that clock-gene disruption causes the full metabolic syndrome.


2021 ◽  
Vol 7 (1) ◽  
pp. e000876
Author(s):  
Alireza Basti ◽  
Müge Yalçin ◽  
David Herms ◽  
Janina Hesse ◽  
Ouda Aboumanify ◽  
...  

ObjectivesIn this study, we investigated daily fluctuations in molecular (gene expression) and physiological (biomechanical muscle properties) features in human peripheral cells and their correlation with exercise performance.Methods21 healthy participants (13 men and 8 women) took part in three test series: for the molecular analysis, 15 participants provided hair, blood or saliva time-course sampling for the rhythmicity analysis of core-clock gene expression via RT-PCR. For the exercise tests, 16 participants conducted strength and endurance exercises at different times of the day (9h, 12h, 15h and 18h). Myotonometry was carried out using a digital palpation device (MyotonPRO), five muscles were measured in 11 participants. A computational analysis was performed to relate core-clock gene expression, resting muscle tone and exercise performance.ResultsCore-clock genes show daily fluctuations in expression in all biological samples tested for all participants. Exercise performance peaks in the late afternoon (15–18 hours for both men and women) and shows variations in performance, depending on the type of exercise (eg, strength vs endurance). Muscle tone varies across the day and higher muscle tone correlates with better performance. Molecular daily profiles correlate with daily variation in exercise performance.ConclusionTraining programmes can profit from these findings to increase efficiency and fine-tune timing of training sessions based on the individual molecular data. Our results can benefit both professional athletes, where a fraction of seconds may allow for a gold medal, and rehabilitation in clinical settings to increase therapy efficacy and reduce recovery times.


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