Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and zeitgeber activity of training in mouse muscle

Maier, Geraldine; Delezie, Julien; Westermark, Pål O.; Santos, Gesa; Ritz, Danilo; Handschin, Christoph

doi:10.1113/jp281535

Cited by 35 publications

(43 citation statements)

References 93 publications

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“…4E), three (Pgm1-Ser 117 , Pgm1-Thr 115 , Pgm1-Thr 19 ) were increased at the pre timepoint 1.7-, 3-, and 5.5-fold, respectively. Phosphorylation levels on these sites were then uniformly decreased immediately following exercise (similar to recent findings in exercised rodents - Maier et al 2021), followed by a sharp increase at the 1hrp timepoint - all of which were greater in the cavefish (Fig 4E and 4F). These findings indicate that in both basal and recovery states, cavefish have hyperphosphorylation of Pgm1 relative to surface fish - suggesting phosphorylation of Pgm1 is a crucial node in cavefish glycogen metabolism.…”

Section: Resultssupporting

confidence: 84%

“…2K). These findings support our recent discovery of Tinaja, Pachón, and Molino cavefish encoding a truncated variant of Period 2 -affecting its inhibitory pparγ-binding domain -a variant we validated is present in cavefish skeletal muscle (Xiong et al 2021). Congruently, cavefish muscle had elevated expression of the lipid metabolism genes adiponectin b (adipoqb), ceramide synthase 4-b (cers4b), adiponutrin (pnpla3), and leptin receptor (lepr) (Fig.…”

Section: Cavefish Show Increased Expression Of Genes Involved In Skel...supporting

confidence: 87%

“…1B and S1A), we hypothesized that their skeletal muscle would reflect an "inactive" phenotype, and hence shift investment away from muscle mass and instead toward fat accumulation. To this point, baseline A. mexicanus body composition was gathered using an echo magnetic resonance imaging (echoMRI) system (Xiong et al 2021). Supporting our hypothesis, we found both Pachón and Tinaja cavefish have ~2.5-fold less lean mass (Fig.…”

Section: Shift In Swimming Speed and Body Composition Following Cave ...supporting

confidence: 72%

“…sarcomeric proteins actin and myosin) (Roberts et al 2020). Because cavefish can store considerable energy reserves throughout their body (Xiong et al 2021), we reasoned their muscle fiber growth arises through sarcoplasmic hypertrophy at the expense of myofibrillar hypertrophy -specifically via accumulation of sugars and fats. Supporting our hypothesis, we found cavefish skeletal muscle had ~4-fold greater triglyceride levels (Fig.…”

Section: Shift In Swimming Speed and Body Composition Following Cave ...mentioning

confidence: 99%

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Metabolic reprogramming underlies cavefish muscular endurance despite loss of muscle mass and contractility

Olsen

Levy

Medley

et al. 2022

Preprint

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Physical inactivity - specifically the lack of moderate-to-vigorous activity — is a scourge to human health, promoting metabolic disease and muscle wasting. Interestingly, multiple ecological niches have relaxed investment into physical activity, providing unique evolutionary insight into adaptive physical inactivity. The Mexican cavefish Astyanax mexicanus lost moderate-to-vigorous activity following cave colonization, reaching basal swim speeds ~3-fold slower than their river-dwelling counterpart. We found that this was accompanied by a marked shift in body composition, decreasing muscle mass by 30% and increasing fat mass by 40%. This shift persisted at the single muscle fiber level via increased lipid and sugar accumulation at the expense of myofibrillar volume. Transcriptomic analysis of laboratory-reared and wild-caught cavefish indicated this shift in investment is driven by increased expression of pparγ — the master regulator of adipogenesis — with a simultaneous decrease in fast myosin heavy chain expression. Ex vivo and in vivo analysis confirmed these investment strategies come with a functional trade-off, decreasing cavefish muscle fiber shortening velocity, time to maximal force, and ultimately maximal swimming velocity. Despite this, cavefish displayed a striking degree of muscular endurance, reaching maximal swim speeds ~3.5-fold faster than their basal swim speeds. Multi-omics analysis indicated metabolic reprogramming, specifically increased phosphoglucomutase-1 abundance, phosphorylation, and activity, as contributing mechanisms enhancing cavefish glycogen utilization under metabolically strenuous conditions. Collectively, we reveal broad skeletal muscle reprogramming following cave colonization, displaying an adaptive skeletal muscle phenotype reminiscent to mammalian disuse and high-fat models while simultaneously maintaining a unique capacity for sustained muscle contraction under fatiguing conditions.

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Section: Resultssupporting

confidence: 84%

Section: Cavefish Show Increased Expression Of Genes Involved In Skel...supporting

confidence: 87%

Section: Shift In Swimming Speed and Body Composition Following Cave ...supporting

confidence: 72%

Section: Shift In Swimming Speed and Body Composition Following Cave ...mentioning

confidence: 99%

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Metabolic reprogramming underlies cavefish muscular endurance despite loss of muscle mass and contractility

Olsen

Levy

Medley

et al. 2022

Preprint

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“…Given the significant impact of genetically deleting both of the circadian repressors Cry1 and Cry2 on maximum treadmill running speed in mice [17], we hypothesized that maximum sprint speed may depend on the time of day. Others have reported that sedentary male mice exhibit enhanced sprint exercise capacity early in the night when CRY1/2 protein expression is lower [6] or at the dark to light transition [25]. However, we did not detect any significant impact of time of day on maximum sprint speed in sedentary c57BL/6J male mice (Figures 1B, 1C, and S1B).…”

Section: Resultscontrasting

confidence: 62%

Daily running enhances molecular and physiological circadian rhythms in skeletal muscle

Duglan

Vallve²,

Vaughan³

et al. 2020

Preprint

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Identifying molecular adaptations underlying improved fitness in response to training is of critical interest in exercise physiology. Circadian rhythms broadly modulate metabolism, including muscle substrate utilization and exercise capacity. Here we show that time of day influences the increase in exercise capacity afforded by training: when maximum running speed is measured at the beginning of the nighttime active period in mice, there is no measurable benefit from training, while maximum increase in performance occurs at the end of the night. Incidentally, we describe an improved method to motivate running in rodent exercise studies that obviates the use of electrical stimulation. Furthermore, we describe daily rhythms in carbohydrate and lipid metabolism and transport associated with the time-dependent response to training. Thus, we show that circadian rhythms modulate muscle-intrinsic responses to training and provide resources for the optimal design of exercise studies in rodents.

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Exercise-Regulated Mitochondrial and Nuclear Signalling Networks in Skeletal Muscle

Reisman,

Hawley,

Hoffman

2024

Sports Med

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Exercise perturbs energy homeostasis in skeletal muscle and engages integrated cellular signalling networks to help meet the contraction-induced increases in skeletal muscle energy and oxygen demand. Investigating exercise-associated perturbations in skeletal muscle signalling networks has uncovered novel mechanisms by which exercise stimulates skeletal muscle mitochondrial biogenesis and promotes whole-body health and fitness. While acute exercise regulates a complex network of protein post-translational modifications (e.g. phosphorylation) in skeletal muscle, previous investigations of exercise signalling in human and rodent skeletal muscle have primarily focused on a select group of exercise-regulated protein kinases [i.e. 5ʹ adenosine monophosphate-activated protein kinase (AMPK), protein kinase A (PKA), Ca2+/calmodulin-dependent protein kinase (CaMK) and mitogen-activated protein kinase (MAPK)] and only a small subset of their respective protein substrates. Recently, global mass spectrometry-based phosphoproteomic approaches have helped unravel the extensive complexity and interconnection of exercise signalling pathways and kinases beyond this select group and phosphorylation and/or translocation of exercise-regulated mitochondrial and nuclear protein substrates. This review provides an overview of recent advances in our understanding of the molecular events associated with acute endurance exercise-regulated signalling pathways and kinases in skeletal muscle with a focus on phosphorylation. We critically appraise recent evidence highlighting the involvement of mitochondrial and nuclear protein phosphorylation and/or translocation in skeletal muscle adaptive responses to an acute bout of endurance exercise that ultimately stimulate mitochondrial biogenesis and contribute to exercise’s wider health and fitness benefits.

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Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and zeitgeber activity of training in mouse muscle

Cited by 35 publications

References 93 publications

Metabolic reprogramming underlies cavefish muscular endurance despite loss of muscle mass and contractility

Metabolic reprogramming underlies cavefish muscular endurance despite loss of muscle mass and contractility

Daily running enhances molecular and physiological circadian rhythms in skeletal muscle

Exercise-Regulated Mitochondrial and Nuclear Signalling Networks in Skeletal Muscle

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