bims-exemet 2021-05-09 papers

bims-exemet

Biomed News

on Exercise metabolism

Issue of 2021–05–09
ten papers selected by
Javier Botella Ruiz, Victoria University

Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans.
Maternal exercise during pregnancy modulates mitochondrial function and redox status in a sex-dependent way in adult offspring's skeletal muscle.
Zeitgebers of skeletal muscle and implications for metabolic health.
High-intensity exercise training - too much of a good thing?
Too much of a good thing: Excess exercise can harm mitochondria.
Mechanisms of exercise as a preventative measure to muscle wasting.
High-frequency blood flow restricted resistance exercise results in acute and prolonged cellular stress more pronounced in type I than in type II fibers.
The effects of exercise training on Kinesin and GAP-43 expression in skeletal muscle fibers of STZ-induced diabetic rats.
Regular aerobic exercise increased VEGF levels in both soleus and gastrocnemius muscles correlated with hippocampal learning and VEGF levels.
Decreased muscle-derived musclin by chronic resistance exercise is associated with improved insulin resistance in rats with type 2 diabetes.

J Cachexia Sarcopenia Muscle. 2021 May 05.

Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans.

Colleen S Deane, Craig R G Willis, Bethan E Phillips, Philip J Atherton, Lorna W Harries, Ryan M Ames, Nathaniel J Szewczyk, Timothy Etheridge.

   BACKGROUND: Skeletal muscle atrophy manifests across numerous diseases; however, the extent of similarities/differences in causal mechanisms between atrophying conditions in unclear. Ageing and disuse represent two of the most prevalent and costly atrophic conditions, with resistance exercise training (RET) being the most effective lifestyle countermeasure. We employed gene-level and network-level meta-analyses to contrast transcriptomic signatures of disuse and RET, plus young and older RET to establish a consensus on the molecular features of, and therapeutic targets against, muscle atrophy in conditions of high socio-economic relevance.
METHODS: Integrated gene-level and network-level meta-analysis was performed on publicly available microarray data sets generated from young (18-35 years) m. vastus lateralis muscle subjected to disuse (unilateral limb immobilization or bed rest) lasting ≥7 days or RET lasting ≥3 weeks, and resistance-trained older (≥60 years) muscle.
RESULTS: Disuse and RET displayed predominantly separate transcriptional responses, and transcripts altered across conditions were mostly unidirectional. However, disuse and RET induced directly inverted expression profiles for mitochondrial function and translation regulation genes, with COX4I1, ENDOG, GOT2, MRPL12, and NDUFV2, the central hub components of altered mitochondrial networks, and ZMYND11, a hub gene of altered translation regulation. A substantial number of genes (n = 140) up-regulated post-RET in younger muscle were not similarly up-regulated in older muscle, with young muscle displaying a more pronounced extracellular matrix (ECM) and immune/inflammatory gene expression response. Both young and older muscle exhibited similar RET-induced ubiquitination/RNA processing gene signatures with associated PWP1, PSMB1, and RAF1 hub genes.
CONCLUSIONS: Despite limited opposing gene profiles, transcriptional signatures of disuse are not simply the converse of RET. Thus, the mechanisms of unloading cannot be derived from studying muscle loading alone and provides a molecular basis for understanding why RET fails to target all transcriptional features of disuse. Loss of RET-induced ECM mechanotransduction and inflammatory profiles might also contribute to suboptimal ageing muscle adaptations to RET. Disuse and age-dependent molecular candidates further establish a framework for understanding and treating disuse/ageing atrophy.

Keywords:  Ageing; Gene-level analysis; Network analysis; Resistance exercise training; Skeletal muscle disuse; Transcriptomic meta-analysis

DOI:  https://doi.org/10.1002/jcsm.12706
J Dev Orig Health Dis. 2021 May 05. 1-8

Maternal exercise during pregnancy modulates mitochondrial function and redox status in a sex-dependent way in adult offspring's skeletal muscle.

R M Hözer, B G Dos Santos, P M August, K S Rodrigues, R M Maurmann, E B Flores, C Matté.

  Maternal exercise has shown beneficial effects on mother and child. Literature confirm progeny's cognition improvement, and upregulation in neurotrophins, antioxidant network, and DNA repair system. Considering that there is a lack of information demonstrating the impact of maternal exercise on offspring's skeletal muscle, we aimed to investigate the mitochondrial and redox effects elicited by maternal swimming. Adult female Wistar rats were divided into three groups: control sedentary, free swimming, and swimming with overload (2% of the body weight). Exercised groups were submitted weekly to five swimming sessions (30 min/day), starting 1 week prior to the mating and lasting to the delivery. Gastrocnemius and soleus muscle from 60-day-old offspring were analyzed. Our results clearly showed a sex-dependent effect. Male soleus showed increased mitochondrial functionality in the overload group. Female muscle from the overload group adapted deeply. Considering the redox status, the female offspring delivered to overload exercised dams presented reduced oxidants levels and protein damage, allied to downregulated antioxidant defenses. We also observed an increase in the mitochondrial function in the gastrocnemius muscle of the female offspring born from overload exercised dams. Soleus from female delivered to the overload exercise group presented reduced mitochondrial activity, as well as reduced reactive species, protein carbonyls, and antioxidant network, when compared to the male. In conclusion, maternal exercise altered the redox status and mitochondrial function in the offspring's skeletal muscle in a sex-dependent way. The clinical implication was not investigated; however, the sexual dimorphism in response to maternal exercise might impact exercise resilience in adulthood.

Keywords:  Maternal exercise; antioxidant; mitochondria; redox status; sexual dimorphism; skeletal muscle

DOI:  https://doi.org/10.1017/S2040174421000209
J Physiol. 2021 May 07.

Zeitgebers of skeletal muscle and implications for metabolic health.

Brendan M Gabriel, Juleen R Zierath.

  Metabolic health is a crucial area of current research, and is an outcome of innate physiology, and interactions with the environment. Environmental cues, such as the Earth's day-night rhythm, partly regulate diurnal hormones and metabolites. Circadian physiology consists of highly conserved biological processes over ∼24-hour cycles, which are influenced by external cues (Zeitgebers - "time-keepers"). Skeletal muscle has diurnal variations of a large magnitude, owing in part to the strong nature of physical activity throughout the day and other external Zeitgebers. The orchestration of whole-body, and skeletal muscle metabolism is a complex, finely-tuned process, and molecular diurnal variations are regulated by a transcription-translation feedback loop controlled by the molecular clock, as well as non-transcriptional metabolic processes. The mitochondrion may play an important role in regulating diurnal metabolites within skeletal muscle, given its central role in the regulation of NAD+ /NADH, O2, reactive oxygen species and redox metabolism. These molecular pathways display diurnal variation and illustrate the complex orchestration of circadian metabolism in skeletal muscle. Probably the most robust Zeitgeber of skeletal muscle is exercise, which alters glucose metabolism and flux, in addition to a range of other diurnal metabolic pathways. Indeed, performing exercise at different times of the day may alter metabolism and health outcomes in some cohorts. The objective of this Symposium Review is to briefly cover the current literature, and to speculate regarding future areas of research. Thus, we postulate that metabolic health may be optimized by altering the timing of external cues such as diet and exercise. This article is protected by copyright. All rights reserved.

Keywords:

DOI:  https://doi.org/10.1113/JP280884
Nat Rev Endocrinol. 2021 May 04.

High-intensity exercise training - too much of a good thing?

John A Hawley, David J Bishop.

DOI: https://doi.org/10.1038/s41574-021-00500-6
Cell Metab. 2021 May 04. pii: S1550-4131(21)00174-1. [Epub ahead of print]33(5): 847-848

Too much of a good thing: Excess exercise can harm mitochondria.

Mark W Pataky, K Sreekumaran Nair.

Health benefits of aerobic exercise are indisputable and are closely related to the maintenance of mitochondrial energy homeostasis and insulin sensitivity. Flockhart et al. (2021) demonstrate, however, that a high volume of high-intensity aerobic exercise adversely affects mitochondrial function and may cause impaired glucose tolerance.

DOI: https://doi.org/10.1016/j.cmet.2021.04.008
Am J Physiol Cell Physiol. 2021 May 05.

Mechanisms of exercise as a preventative measure to muscle wasting.

Zachary A Graham, Kaleen M Lavin, Samia O'Bryan, Anna Thalacker-Mercer, Thomas W Buford, Kenneth M Ford, Timothy J Broderick, Marcas M Bamman.

  Skeletal muscle is the most abundant tissue in healthy individuals and it has important roles in health beyond voluntary movement. The overall mass and energy requirements of skeletal muscle require it to be metabolically active and flexible to multiple energy substrates. The tissue has evolved to be largely load-dependent and it readily adapts in a number of positive ways to repetitive overload, such as various forms of exercise training. However, unloading from extended bed rest and/or metabolic derangements in response to trauma, acute illness, or severe pathology, commonly result in rapid muscle wasting. Declines in muscle mass contribute to multi-morbidity, reduce function and exert a substantial, negative impact on quality of life. The principal mechanisms controlling muscle mass have been well-described and these cellular processes are intricately regulated by exercise. Accordingly, exercise has shown great promise and efficacy in preventing or slowing muscle wasting through changes in molecular physiology, organelle function, cell signaling pathways and epigenetic regulation. In this review we focus on the role of exercise in altering the molecular landscape of skeletal muscle in a manner that improves or maintains its health and function in the presence of unloading or disease.

Keywords:  epigenetics; exercise; muscle wasting; resistance training; skeletal muscle

DOI:  https://doi.org/10.1152/ajpcell.00056.2021
J Appl Physiol (1985). 2021 May 06.

High-frequency blood flow restricted resistance exercise results in acute and prolonged cellular stress more pronounced in type I than in type II fibers.

Thomas Bjørnsen, Mathias Wernbom, Goran Paulsen, James F Markworth, Sveinung Berntsen, Randall F D'Souza, David Cameron-Smith, Truls Raastad.

  Myocellular stress with high-frequency blood flow restricted resistance exercise (BFRRE) was investigated by measures of heat shock protein (HSP) responses, glycogen content and inflammatory markers. Thirteen participants (24±2 years [mean±SD], 9 males) completed two 5-day-blocks of 7 BFRRE sessions, separated by 10 days. Four sets of unilateral knee extensions to failure at 20% of 1RM were performed. Muscle samples obtained before, 1h after the first session in the first and second block ("Acute1" and "Acute2"), after 3 sessions ("Day4"), during the "Rest Week", and at 3 ("Post3") and 10 days post-intervention ("Post10"), were analyzed for HSP70, αB-crystallin, glycogen (PAS staining), mRNAs, miRNAs, and CD68+ (macrophages) and CD66b+ (neutrophils) cell numbers. αB-crystallin translocated from the cytosolic to the cytoskeletal fraction after Acute1 and Acute2 (p<0.05), and immunostaining revealed larger responses in type I than type II fibers (Acute1, 225±184% vs. 92±81%, respectively, p=0.001). HSP70 was increased in the cytoskeletal fraction at Day4 and Post3, and immunostaining intensities were more elevated in type I than in type II fibers at Day4, (206±84% vs. 72±112%, respectively, p<0.001), during the Rest Week (98±66% vs. 42±79%, p<0.001) and at Post3 (115±82% vs. 28±78%, p=0.003). Glycogen content was reduced in both fiber types; but most pronounced in type I, which did not recover until the Rest Week (-15-29%, p≤0.001). Intramuscular macrophage numbers were increased by ~65% post-intervention, but no changes were observed in muscle neutrophils. We conclude that high-frequency BFRRE with sets performed till failure stresses both fiber types, with type I fibers being most affected.

Keywords:  Glycogen staining; Inflammation; Kaatsu; Muscle damage; Stress proteins

DOI:  https://doi.org/10.1152/japplphysiol.00115.2020
Sci Rep. 2021 May 05. 11(1): 9535

The effects of exercise training on Kinesin and GAP-43 expression in skeletal muscle fibers of STZ-induced diabetic rats.

Masoud Rahmati, Seyed Jalal Taherabadi.

Kinesin-1 and Growth Associated Protein 43 (GAP-43) localization in muscle fiber are crucial for proper skeletal muscle hypertrophy. To evaluate this assumption, we investigated the beneficial effects of endurance training on GAP-43 and Kinesin Family Member 5B (KIF5B) expression in gastrocnemius muscle of streptozotocin (STZ)-induced diabetic rats. Fifty-two male rats were randomly divided into four groups: healthy control (C), healthy trained (T), diabetic control (DC) and diabetic trained (DT). Diabetes was induced by a single intraperitoneal injection of STZ (45 mg/kg). The rats in DT and T groups were subjected to treadmill running for 5 days a week over 6 weeks. The results indicated that the GAP-43 and KIF5B protein levels in the DC group were significantly lower than those in the C group. Additionally, chronic treadmill running in diabetic rats was accompanied by significant increase of GAP-43 and KIF5B protein expression, compared to DC group. Furthermore, the endurance training in healthy rats was associated with a significant increase of GAP-43 and KIF5B protein levels. In addition, we found positive correlation between GAP-43 and KIF5B protein levels and myonuclear number per fiber and average gastrocnemius cross-sectional area (CSA). GAP43 and KIF5B protein levels were decreased in skeletal muscles of diabetic rats, and exercise training had beneficial effects and could restore their abnormal expression. Moreover, there is a strong relationship between muscle hypertrophy and GAP-43 and KIF5B protein levels.

DOI: https://doi.org/10.1038/s41598-021-89106-6
Acta Neurobiol Exp (Wars). 2021 ;81(1): 1-9

Regular aerobic exercise increased VEGF levels in both soleus and gastrocnemius muscles correlated with hippocampal learning and VEGF levels.

Asli Karakilic, Oguz Yuksel, Servet Kizildag, Ferda Hosgorler, Birsu Topcugil, Rabia Ilgin, Hikmet Gumus, Guven Guvendi, Basar Koc, Sevim Kandis, Mehmet Ates, Nazan Uysal.

Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis.
Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis.

DOI: https://doi.org/10.21307/ane-2021-001
Physiol Rep. 2021 May;9(9): e14823

Decreased muscle-derived musclin by chronic resistance exercise is associated with improved insulin resistance in rats with type 2 diabetes.

Mio Shimomura, Naoki Horii, Shumpei Fujie, Kenichiro Inoue, Natsuki Hasegawa, Keiko Iemitsu, Masataka Uchida, Motoyuki Iemitsu.

  Chronic resistance exercise induces improved hyperglycemia in patients with type 2 diabetes mellitus. Musclin, a muscle-derived secretory factor, is involved in the induction of insulin resistance via the downregulation of the glucose transporter-4 (GLUT-4) signaling pathway in skeletal muscles. However, whether musclin affects the mechanism of resistance exercise remains unclear. This study aimed to clarify whether decreased muscle-derived musclin secretion in chronic resistance exercise is involved in the improvement of insulin resistance via the GLUT-4 signaling pathway in rats with type 2 diabetes. Male, 20-week-old, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, were randomly divided into two groups: sedentary control (OLETF-Con) and chronic resistance exercise (OLETF-RT; climbing a ladder three times a week on alternate days for 8 weeks), whereas Long-Evans Tokushima Otsuka rats were used as the nondiabetic sedentary control group. OLETF-Con rats showed increased fasting glucose levels, decreased insulin sensitivity index (QUICKI), muscle GLUT-4 translocation, and protein kinase B (Akt) phosphorylation, and concomitantly increased muscle musclin expression. In contrast, OLETF-RT rats significantly reduced muscle musclin expression, improved hyperglycemia, and QUICKI through an accelerated muscle GLUT-4/Akt signaling pathway. Moreover, chronic resistance exercise-induced reduction of muscle musclin was correlated with changes in fasting glucose, QUICKI, GLUT-4 translocation, and Akt phosphorylation. These findings suggest that the reduction in muscle-derived musclin production by chronic resistance exercise may be involved in improved insulin resistance in rats with type 2 diabetes.

Keywords:  insulin resistance; musclin; resistance exercise; type 2 diabetes

DOI:  https://doi.org/10.14814/phy2.14823