Daily running enhances molecular and physiological circadian rhythms in skeletal muscle

Casanova-Vallve, Nuria; Duglan, Drew; Vaughan, Megan; Pariollaud, Marie; Handzlik, Michal K.; Fan, Weiwei; Yu, Ruth T.; Liddle, Christopher; Downes, Michael; Delezie, Julien; Mello, Rebecca; Chan, Alanna B.; Westermark, Pål O.; Metallo, Christian M.; Evans, Ronald M.; Lamia, Katja

doi:10.1016/j.molmet.2022.101504

Cited by 22 publications

(19 citation statements)

References 78 publications

(107 reference statements)

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“…The ChIP-seq also revealed a potential interaction with Ankrd1 (78) that did not emerge in our musclespecific MYC overexpression experiment. Lower levels of Reverbs during overload could have implications for circadian regulation and metabolism in muscle fibers (81); this is salient since MYC is exercise-responsive and exercise shifts the circadian rhythm in skeletal muscle (90)(91)(92)(93). Perhaps an exercise-mediated shift in muscle circadian rhythm is controlled by MYC, but more work is needed in this area, especially with respect to resistance exercise.…”

Section: Discussionmentioning

confidence: 99%

Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Murach¹,

Liu²,

Jude³

et al. 2022

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Murach¹,

Liu²,

Jude³

et al. 2022

Journal of Biological Chemistry

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“…Compared with healthy individuals, obese individuals had a significantly higher fasting glucose level (Figure 1C), insulin level (Figure 1D), and HOMA‐IR index (Figure 1E), suggesting greater insulin resistance in the obese patients than healthy individuals. Skeletal muscle is the most important organ for peripheral glucose utilization and insulin resistance 24 . Therefore, we performed RNA sequencing analysis of muscle tissues from obese and healthy individuals.…”

Section: Resultsmentioning

confidence: 99%

“…Skeletal muscle is the most important organ for peripheral glucose utilization and insulin resistance. 24 Therefore, we performed RNA sequencing analysis of muscle tissues from obese and healthy individuals. Our results showed that HSF1 expression was significantly decreased in the muscle tissues of obese individuals (Figure 1F).…”

Section: Hsf1 Levelmentioning

confidence: 99%

Skeletal muscle HSF1 prevents insulin resistance by improving glucose utilization

Lin

et al. 2022

The FASEB Journal

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The regulation of muscle glucose utilization has significant potential for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Heat shock factor 1 (HSF1) is involved in cellular metabolism and regulation of muscle metabolism. However, it is unclear how HSF1 regulates muscle glucose metabolism. In the present study, the development of obesity in mice was associated with HSF1 downregulation. Serum samples and muscle biopsies were obtained from obese and healthy humans. Fasting glucose and insulin levels and the homeostasis model assessment of insulin resistance value showed that obesity was associated with insulin resistance. The skeletal muscle level of HSF1 was decreased in obese and ob/ob mice. HSF1 was selectively over-expressed in the skeletal muscles of high fat diet (HFD)-fed mice. Muscle HSF1 over-expression successfully triggered glycolytic-to-oxidative myofiber switch and increased fatty acid metabolism and insulin sensitivity in the skeletal muscles of HFD-fed mice. Moreover, HSF1 improved energy expenditure and blocked muscle accumulation of triglycerides in HFD-fed mice. Consequently, muscle HSF1 mitigated the impaired muscle insulin signaling and insulin resistance in HFD-fed mice. In conclusion, T2DM and obesity in HFD-fed mice may be treated with selective HSF1-directed programming of exercise-like effects in skeletal muscle. These findings may aid the development of a new therapeutic approach for obesity and T2DM.

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“…In skeletal muscle, in addition to maintenance of nutrient metabolism and structural integrity, the circadian clock is intimately involved in modulation of muscle stem cell myogenic properties in tissue growth processes (6,28,29). A functional muscle clock is required to facilitate metabolic fuel switch from fat oxidation to glucose utilization as a nutrient sensor that determines insulin sensitivity by responding to feeding signals (30), and this metabolic role of the muscle clock was also highlighted by recent findings of augmented metabolic rhythm by exercise regimen (29,31). Our previous studies revealed that the clock is required to orchestrate myogenic progression of muscle stem cells (32)(33)(34)(35).…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating studies indicate that circadian clock exert important temporal control in distinct aspects governing stem cell behaviors (7, 8, 26, 27). In skeletal muscle, in addition to maintenance of nutrient metabolism and structural integrity, the circadian clock is intimately involved in modulation of muscle stem cell myogenic properties in tissue growth processes (6, 28, 29). A functional muscle clock is required to facilitate metabolic fuel switch from fat oxidation to glucose utilization as a nutrient sensor that determines insulin sensitivity by responding to feeding signals (30), and this metabolic role of the muscle clock was also highlighted by recent findings of augmented metabolic rhythm by exercise regimen (29, 31).…”

Section: Introductionmentioning

confidence: 99%

Targeted Screening and Identification of Chlorhexidine as a Pro-myogenic Circadian Clock Activator

Kiperman

et al. 2023

Preprint

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Background: Circadian clock is an evolutionarily-conserved mechanism that exerts pervasive temporal control in stem cell behavior. This time-keeping machinery is required for orchestrating myogenic progenitor properties in regenerative myogenesis that ameliorates muscular dystrophy. Here we report a screening platform to discover circadian clock modulators that promote myogenesis, with the identification of chlorhexidine (CHX) as a clock-activating molecule with pro-myogenic activities. Methods: A high-throughput molecular docking pipeline was applied to identify candidate compounds with a structural fit for a hydrophobic pocket within the key circadian transcription factor protein, Circadian Locomotor Output Cycles Kaput (CLOCK). Secondary biochemical screen for clock-modulatory activities of these molecules were preformed, together with functional validations of myogenic regulations to identify modulators with pro-myogenic properties. Results: CHX was identified as a clock activator that promotes distinct aspects of myogenesis. CHX activated circadian clock that reduced cycling period length and augmented amplitude. This action was mediated by the targeted CLOCK structure via augmented interaction with heterodimer partner Bmal1, leading to enhanced CLOCK/Bmal1-controlled transcription with up-regulation of core clock genes. Consistent with its clock-activating function, CHX displayed robust effects on stimulating myogenic differentiation in a clock-dependent manner. In addition, CHX augmented the proliferative and migratory activities of myoblasts. Conclusion: Our findings demonstrate the feasibility of a screening platform to discover clock modulators with myogenic regulatory activities. Discovery of CHX as a pro-myogenic molecule could be applicable to promote regenerative capacities in ameliorating dystrophic or degenerative muscle diseases.

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Daily running enhances molecular and physiological circadian rhythms in skeletal muscle

Cited by 22 publications

References 78 publications

Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Skeletal muscle HSF1 prevents insulin resistance by improving glucose utilization

Targeted Screening and Identification of Chlorhexidine as a Pro-myogenic Circadian Clock Activator

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