Ticking for Metabolic Health:The Skeletal-Muscle Clocks

To be prepared for alternating metabolic demands occurring over the 24-hour day, the body preserves information on time in skeletal muscle, and all cells, through a circadian clock mechanism. Skeletal muscle can be considered the largest collection of peripheral clocks in the body with a major contribution to whole body energy metabolism. Comparison of circadian clock gene expression between skeletal muscle of nocturnal rodents and diurnal humans reveals very common patterns based on rest/active cycles rather than light/dark cycles. Rodent studies in which the circadian clock is disrupted in skeletal muscle demonstrate impaired glucose handling and insulin resistance. Experimental circadian misalignment in humans modifies the skeletal muscle clocks and leads to disturbed energy metabolism and insulin resistance. Preclinical studies have revealed that timing of exercise over the day can influence the beneficial effects of exercise on skeletal muscle metabolism and studies suggest similar applicability in humans. Current strategies to improve metabolic health, e.g. exercise, should be reinvestigated in their capability to modify the skeletal muscle clocks by taking timing of the intervention into account

ISCHEMIC PRECONDITIONING BLUNTS ECCENTRIC EXERCISE-INDUCED MUSCLE DAMAGE DUE TO REDUCED OXIDATIVE STRESS?

The purpose of this study was to investigate if ischemic preconditioning (IPC) prior to eccentric exercise of the elbow flexors leads to alterations in muscle oxygen saturation (SmO2) during loading. Additionally, parameters of muscle damage, like serum creatine kinase, were assessed following the loading protocol. Nineteen untrained males were allocated into two groups: (1) performing IPC prior to eccentric exercise (IPC+ECC; n=10) and (2) performing eccentric exercise only (n=9). Muscle damage parameters were significantly lower in IPC+ECC (p2 during eccentric loading (ischemia) as well as the subsequent increase of SmO2 (reperfusion) were lower in IPC+ECC (

The influence of bright and dim light on substrate metabolism, energy expenditure and thermoregulation in insulin-resistant individuals depends on time of day

AIMS/HYPOTHESIS: In our modern society, artificial light is available around the clock and most people expose themselves to electrical light and light-emissive screens during the dark period of the natural light/dark cycle. Such suboptimal lighting conditions have been associated with adverse metabolic effects, and redesigning indoor lighting conditions to mimic the natural light/dark cycle more closely holds promise to improve metabolic health. Our objective was to compare metabolic responses to lighting conditions that resemble the natural light/dark cycle in contrast to suboptimal lighting in individuals at risk of developing metabolic diseases. METHODS: Therefore, we here performed a non-blinded, randomised, controlled, crossover trial in which overweight insulin-resistant volunteers (n = 14) were exposed to two 40 h laboratory sessions with different 24 h lighting protocols while staying in a metabolic chamber under real-life conditions. In the Bright day–Dim evening condition, volunteers were exposed to electric bright light (~1250 lx) during the daytime (08:00–18:00 h) and to dim light (~5 lx) during the evening (18:00–23:00 h). Vice versa, in the Dim day–Bright evening condition, volunteers were exposed to dim light during the daytime and bright light during the evening. Randomisation and allocation to light conditions were carried out by sequential numbering. During both lighting protocols, we performed 24 h indirect calorimetry, and continuous core body and skin temperature measurements, and took frequent blood samples. The primary outcome was plasma glucose focusing on the pre- and postprandial periods of the intervention. RESULTS: Spending the day in bright light resulted in a greater increase in postprandial triacylglycerol levels following breakfast, but lower glucose levels preceding the dinner meal at 18:00 h, compared with dim light (5.0 ± 0.2 vs 5.2 ± 0.2 mmol/l, n = 13, p=0.02). Dim day–Bright evening reduced the increase in postprandial glucose after dinner compared with Bright day–Dim evening (incremental AUC: 307 ± 55 vs 394 ± 66 mmol/l × min, n = 13, p=0.009). After the Bright day–Dim evening condition the sleeping metabolic rate was identical compared with the baseline night, whereas it dropped after Dim day–Bright evening. Melatonin secretion in the evening was strongly suppressed for Dim day–Bright evening but not for Bright day–Dim evening. Distal skin temperature for Bright day–Dim evening was lower at 18:00 h (28.8 ± 0.3°C vs 29.9 ± 0.4°C, n = 13, p=0.039) and higher at 23:00 h compared with Dim day–Bright evening (30.1 ± 0.3°C vs 28.8 ± 0.3°C, n = 13, p=0.006). Fasting and postprandial plasma insulin levels and the respiratory exchange ratio were not different between the two lighting protocols at any time. CONCLUSIONS/INTERPRETATION: Together, these findings suggest that the indoor light environment modulates postprandial substrate handling, energy expenditure and thermoregulation of insulin-resistant volunteers in a time-of-day-dependent manner. TRIAL REGISTRATION: ClinicalTrials.gov NCT03829982. FUNDING: We acknowledge the financial support from the Netherlands Cardiovascular Research Initiative: an initiative with support from the Dutch Heart Foundation (CVON2014–02 ENERGISE). GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05643-9

Ticking for Metabolic Health: The Skeletal‐Muscle Clocks

To be prepared for alternating metabolic demands occurring over the 24-hour day, the body preserves information on time in skeletal muscle, and in all cells, through a circadian-clock mechanism. Skeletal muscle can be considered the largest collection of peripheral clocks in the body, with a major contribution to whole-body energy metabolism. Comparison of circadian-clock gene expression between skeletal muscle of nocturnal rodents and diurnal humans reveals very common patterns based on rest/active cycles rather than light/dark cycles. Rodent studies in which the circadian clock is disrupted in skeletal muscle demonstrate impaired glucose handling and insulin resistance. Experimental circadian misalignment in humans modifies the skeletal-muscle clocks and leads to disturbed energy metabolism and insulin resistance. Preclinical studies have revealed that timing of exercise over the day can influence the beneficial effects of exercise on skeletal-muscle metabolism, and studies suggest similar applicability in humans. Current strategies to improve metabolic health (e.g., exercise) should be reinvestigated in their capability to modify the skeletal-muscle clocks by taking timing of the intervention into account

Neuromuscular Electrical Stimulation Reduces Leg Cramps in Patients With Lumbar Degenerative Disorders:A Randomized Placebo-Controlled Trial

Objectives Lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH) are often accompanied by frequently occurring leg cramps severely affecting patients' life and sleep quality. Recent evidence suggests that neuromuscular electric stimulation (NMES) of cramp-prone muscles may prevent cramps in lumbar disorders. Materials and Methods Thirty-two men and women (63 +/- 9 years) with LSS and/or LDH suffering from cramps were randomly allocated to four different groups. Unilateral stimulation of the gastrocnemius was applied twice a week over four weeks (3 x 6 x 5 sec stimulation trains at 30 Hz above the individual cramp threshold frequency [CTF]). Three groups received either 85%, 55%, or 25% of their maximum tolerated stimulation intensity, whereas one group only received pseudo-stimulation. Results The number of reported leg cramps decreased in the 25% (25 +/- 14 to 7 +/- 4; p = 0.002), 55% (24 +/- 10 to 10 +/- 11; p = 0.014) and 85%NMES (23 +/- 17 to 1 +/- 1; p 0.999). In the 25% and 85%NMES group, this improvement was accompanied by an increased CTF (p < 0.001). Conclusion Regularly applied NMES of the calf muscles reduces leg cramps in patients with LSS/LDH even at low stimulation intensity.ISSN:1094-7159ISSN:1525-140

Invasive assessment of hemodynamic, metabolic and ionic consequences during blood flow restriction training

Purpose: Medically recommended training often faces the dilemma that necessary mechanical intensities for muscle adaptations exceed patients' physical capacity. In this regard, blood flow restriction (BFR) training is becoming increasingly popular because it enables gains in muscle mass and strength despite using low-mechanical loads combined with external venous occlusion. Since the underlying mechanisms are still unknown, we applied invasive measurements during exercise with and without BFR to promote physiological understanding and safety of this popular training technique. Methods: In a randomized cross-over design, ten healthy men (28.1 ± 6.5 years) underwent two trials of unilateral biceps curls either with (BFR) and without BFR (CON). For analysis of changes in intravascular pressures, blood gases, oximetry and electrolytes, an arterial and a venous catheter were placed at the exercising arm before exercise. Arterial and venous blood gases and intravascular pressures were analyzed before, during and 5 min after exercise. Results: Intravascular pressures in the arterial and venous system were more increased during exercise with BFR compared to CON (p < 0.001). Furthermore, arterial and venous blood gas analyses revealed a BFR-induced metabolic acidosis (p < 0.05) with increased lactate production (p < 0.05) and associated elevations in [K+], [Ca2+] and [Na+] (p < 0.001). Conclusion: The present study describes for the first time the local physiological changes during BFR training. While BFR causes greater hypertension in the arterial and venous system of the exercising extremity, observed electrolyte shifts corroborate a local metabolic acidosis with concurrent rises in [K+] and [Na+]. Although BFR could be a promising new training concept for medical application, its execution is associated with comprehensive physiological challenges

Neuromuscular Electrical Stimulation Reduces Leg Cramps in Patients With Lumbar Degenerative Disorders: A Randomized Placebo-Controlled Trial

Objectives Lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH) are often accompanied by frequently occurring leg cramps severely affecting patients' life and sleep quality. Recent evidence suggests that neuromuscular electric stimulation (NMES) of cramp-prone muscles may prevent cramps in lumbar disorders. Materials and Methods Thirty-two men and women (63 +/- 9 years) with LSS and/or LDH suffering from cramps were randomly allocated to four different groups. Unilateral stimulation of the gastrocnemius was applied twice a week over four weeks (3 x 6 x 5 sec stimulation trains at 30 Hz above the individual cramp threshold frequency [CTF]). Three groups received either 85%, 55%, or 25% of their maximum tolerated stimulation intensity, whereas one group only received pseudo-stimulation. Results The number of reported leg cramps decreased in the 25% (25 +/- 14 to 7 +/- 4; p = 0.002), 55% (24 +/- 10 to 10 +/- 11; p = 0.014) and 85%NMES (23 +/- 17 to 1 +/- 1; p 0.999). In the 25% and 85%NMES group, this improvement was accompanied by an increased CTF (p < 0.001). Conclusion Regularly applied NMES of the calf muscles reduces leg cramps in patients with LSS/LDH even at low stimulation intensity

H-reflex and M-wave responses after voluntary and electrically evoked muscle cramping

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Despite the widespread occurrence of muscle cramps, their underlying neurophysiological mechanisms remain unknown. To better understand the etiology of muscle cramps, this study investigated acute effects of muscle cramping induced by maximal voluntary isometric contractions (MVIC) and neuromuscular electrical stimulation (NMES) on the amplitude of Hoffmann reflexes (H-reflex) and compound muscle action potentials (M-wave). Methods: Healthy men (n = 14) and women (n = 3) participated in two identical sessions separated by 7 days. Calf muscle cramping was induced by performing MVIC of the plantar flexors in a prone position followed by 2.5-s NMES over the plantar flexors with increasing frequency and intensity. H-reflexes and M-waves evoked by tibial nerve stimulation in gastrocnemius medialis (GM) and soleus were recorded at baseline, and after MVIC-induced cramps and the NMES protocol. Results: Six participants cramped after MVIC, and H-reflex amplitude decreased in GM and soleus in Session 1 (− 33 ± 32%, − 34 ± 33%, p = 0.031) with a similar trend in Session 2 (5 cramped, p = 0.063), whereas the maximum M-wave was unchanged. After NMES, 11 (Session 1) and 9 (Session 2) participants cramped. H-reflex and M-wave recruitment curves shifted to the left in both sessions and muscles after NMES independent of cramping (p ≤ 0.001). Conclusion: Changes in H-reflexes after a muscle cramp induced by MVIC and NMES were inconsistent. While MVIC-induced muscle cramps reduced H-reflex amplitude, muscle stretch to end cramping was a potential contributing factor. By contrast, NMES may potentiate H-reflexes and obscure cramp-related changes. Thus, the challenge for future studies is to separate the neural consequences of cramping from methodology-based effects

H-reflex and M-wave responses after voluntary and electrically evoked muscle cramping

Purpose Despite the widespread occurrence of muscle cramps, their underlying neurophysiological mechanisms remain unknown. To better understand the etiology of muscle cramps, this study investigated acute effects of muscle cramping induced by maximal voluntary isometric contractions (MVIC) and neuromuscular electrical stimulation (NMES) on the amplitude of Hoffmann reflexes (H-reflex) and compound muscle action potentials (M-wave). Methods Healthy men (n = 14) and women (n = 3) participated in two identical sessions separated by 7 days. Calf muscle cramping was induced by performing MVIC of the plantar flexors in a prone position followed by 2.5-s NMES over the plantar flexors with increasing frequency and intensity. H-reflexes and M-waves evoked by tibial nerve stimulation in gastrocnemius medialis (GM) and soleus were recorded at baseline, and after MVIC-induced cramps and the NMES protocol. Results Six participants cramped after MVIC, and H-reflex amplitude decreased in GM and soleus in Session 1 (- 33 +/- 32%, - 34 +/- 33%, p = 0.031) with a similar trend in Session 2 (5 cramped, p = 0.063), whereas the maximum M-wave was unchanged. After NMES, 11 (Session 1) and 9 (Session 2) participants cramped. H-reflex and M-wave recruitment curves shifted to the left in both sessions and muscles after NMES independent of cramping (