scholarly journals Road to exercise mimetics: targeting nuclear receptors in skeletal muscle

2013 ◽  
Vol 51 (3) ◽  
pp. T87-T100 ◽  
Author(s):  
Weiwei Fan ◽  
Annette R Atkins ◽  
Ruth T Yu ◽  
Michael Downes ◽  
Ronald M Evans
Keyword(s):  
Skeletal Muscle ◽  
Physical Exercise ◽  
Nuclear Receptors ◽  
Beneficial Effects ◽  
The Metabolic Syndrome ◽  
Bona Fide ◽  
Exercise Mimetics ◽  
Exercise Induced ◽  
Muscle Energy Metabolism ◽  
Clinical Conditions

Skeletal muscle is the largest organ in the human body and is the major site for energy expenditure. It exhibits remarkable plasticity in response to physiological stimuli such as exercise. Physical exercise remodels skeletal muscle and enhances its capability to burn calories, which has been shown to be beneficial for many clinical conditions including the metabolic syndrome and cancer. Nuclear receptors (NRs) comprise a class of transcription factors found only in metazoans that regulate major biological processes such as reproduction, development, and metabolism. Recent studies have demonstrated crucial roles for NRs and their co-regulators in the regulation of skeletal muscle energy metabolism and exercise-induced muscle remodeling. While nothing can fully replace exercise, development of exercise mimetics that enhance or even substitute for the beneficial effects of physical exercise would be of great benefit. The unique property of NRs that allows modulation by endogenous or synthetic ligands makes them bona fide therapeutic targets. In this review, we present an overview of the current understanding of the role of NRs and their co-regulators in skeletal muscle oxidative metabolism and summarize recent progress in the development of exercise mimetics that target NRs and their co-regulators.

scholarly journals Physical activity and health, novel concepts and new targets: report from the 12th Conference of the International Research Group on the Biochemistry of Exercise

2004 ◽  
Vol 63 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Matthijs K. C. Hesselink ◽  
Marleen A. van Baak
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Physical Exercise ◽  
Health Effects ◽  
Research Group ◽  
International Research ◽  
Biochemical Basis ◽  
International Research Group ◽  
Exercise Muscle ◽  
Exercise Induced

The present paper is the introductory paper to a series of brief reviews representing the proceedings of a recent conference on ‘The biochemical basis for the health effects of exercise’ organized by the International Research Group on the Biochemistry of Exercise in conjunction with the Nutrition Society. Here the aim is to briefly review and highlight the main innovations presented during this meeting. The following topics were covered during the meeting: exercise signalling pathways controlling fuel oxidation during and after exercise; the fatty acid transporters of skeletal muscle; mechanisms involved in exercise-induced mitochondrial biogenesis in skeletal muscle; new methodologies and insights in the regulation of fat metabolism during exercise; muscle hypertrophy: the signals of insulin, amino acids and exercise; adipose tissue–liver–muscle interactions leading to insulin resistance. In these symposia state-of-the-art knowledge on how physical exercise exerts its effects on health was presented. The fast-growing number of identified pathways and processes involved in the health effects of physical exercise, which were discussed during the meeting, will help to develop tailored physical-activity regimens in the prevention of inactivity-induced deterioration of health.

Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle

2015 ◽  
Vol 118 (8) ◽  
pp. 971-979 ◽  
Author(s):  
Andreas Buch Møller ◽  
Mikkel Holm Vendelbo ◽  
Britt Christensen ◽  
Berthil Forrest Clasen ◽  
Ann Mosegaard Bak ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Physical Exercise ◽  
Light Chain ◽  
Human Skeletal Muscle ◽  
Transgenic Animal ◽  
Dependent Manner ◽  
Healthy Humans ◽  
Transgenic Animal Models ◽  
Exercise Induced

Data from transgenic animal models suggest that exercise-induced autophagy is critical for adaptation to physical training, and that Unc-51 like kinase-1 (ULK1) serves as an important regulator of autophagy. Phosphorylation of ULK1 at Ser555 stimulates autophagy, whereas phosphorylation at Ser757 is inhibitory. To determine whether exercise regulates ULK1 phosphorylation in humans in vivo in a nutrient-dependent manner, we examined skeletal muscle biopsies from healthy humans after 1-h cycling exercise at 50% maximal O2 uptake on two occasions: 1) during a 36-h fast, and 2) during continuous glucose infusion at 0.2 kg/h. Physical exercise increased ULK1 phosphorylation at Ser555 and decreased lipidation of light chain 3B. ULK1 phosphorylation at Ser555 correlated positively with AMP-activated protein kinase-α Thr172 phosphorylation and negatively with light chain 3B lipidation. ULK1 phosphorylation at Ser757 was not affected by exercise. Fasting increased ULK1 and p62 protein expression, but did not affect exercise-induced ULK1 phosphorylation. These data demonstrate that autophagy signaling is activated in human skeletal muscle after 60 min of exercise, independently of nutritional status, and suggest that initiation of autophagy constitutes an important physiological response to exercise in humans.

scholarly journals Exercise Induced Adipokine Changes and the Metabolic Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Saeid Golbidi ◽  
Ismail Laher
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
The Body ◽  
Beneficial Effects ◽  
The Metabolic Syndrome ◽  
Before And After ◽  
Inflammatory State ◽  
Exercise Induced

The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.

scholarly journals Inflammatory Mechanisms Associated with Skeletal Muscle Sequelae after Stroke: Role of Physical Exercise

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Hélio José Coelho Junior ◽  
Bruno Bavaresco Gambassi ◽  
Tiego Aparecido Diniz ◽  
Isabela Maia da Cruz Fernandes ◽  
Érico Chagas Caperuto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Skeletal Muscle ◽  
Physical Exercise ◽  
Muscle Atrophy ◽  
Inflammatory Markers ◽  
The Other ◽  
Stroke Patients ◽  
Beneficial Effects ◽  
Anti Inflammatory

Inflammatory markers are increased systematically and locally (e.g., skeletal muscle) in stroke patients. Besides being associated with cardiovascular risk factors, proinflammatory cytokines seem to play a key role in muscle atrophy by regulating the pathways involved in this condition. As such, they may cause severe decrease in muscle strength and power, as well as impairment in cardiorespiratory fitness. On the other hand, physical exercise (PE) has been widely suggested as a powerful tool for treating stroke patients, since PE is able to regenerate, even if partially, physical and cognitive functions. However, the mechanisms underlying the beneficial effects of physical exercise in poststroke patients remain poorly understood. Thus, in this study we analyze the candidate mechanisms associated with muscle atrophy in stroke patients, as well as the modulatory effect of inflammation in this condition. Later, we suggest the two strongest anti-inflammatory candidate mechanisms, myokines and the cholinergic anti-inflammatory pathway, which may be activated by physical exercise and may contribute to a decrease in proinflammatory markers of poststroke patients.

scholarly journals Does Irisin Link Physical Exercise with Alzheimer’s Disease?

2018 ◽  
Author(s):  
Dewan Md. Sumsuzzman ◽  
Yunho Jin ◽  
Jeonghyun Choi ◽  
Sang-Rae Lee ◽  
Yonggeun Hong
Keyword(s):  
Skeletal Muscle ◽  
Physical Exercise ◽  
Neurodegenerative Diseases ◽  
Telomere Length ◽  
Neurotrophic Factors ◽  
Therapeutic Target ◽  
Potential Role ◽  
Human Diseases ◽  
Nervous Systems ◽  
Beneficial Effects

Irisin, a skeletal muscle-secreted myokine, produced in response to physical exercise, has protective functions in both the central and the peripheral nervous systems, including the regulation of brain-derived neurotrophic factors and modification of telomere length. Such beneficial effects may inhibit or delay the emergence of neurodegenerative diseases, including Alzheimer’s disease (AD). This review is based on the hypothesis that irisin produced by physical exercise helps control AD progression. Herein, we describe the physiology of irisin and its potential role in delaying or preventing AD. Although current and ongoing studies on irisin show promising results, further research is required to clarify its potential as a meaningful therapeutic target for treating human diseases.

scholarly journals Cardiac and skeletal muscle energy metabolism in heart failure: beneficial effects of voluntary activity

2002 ◽  
Vol 56 (2) ◽  
pp. 260-268 ◽  
Author(s):  
E DESOUSA ◽  
P LECHENE ◽  
D FORTIN ◽  
B NGUESSAN ◽  
S BELMADANI ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Voluntary Activity ◽  
Beneficial Effects ◽  
Muscle Energy ◽  
Muscle Energy Metabolism

scholarly journals Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice

2021 ◽  
Vol 22 (5) ◽  
pp. 2635
Author(s):  
Ana P. Pinto ◽  
Alisson L. da Rocha ◽  
Bruno B. Marafon ◽  
Rafael L. Rovina ◽  
Vitor R. Muñoz ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Gastrocnemius Muscle ◽  
Acute Exercise ◽  
Colchicine Treatment ◽  
Heart Tissue ◽  
Beclin 1 ◽  
Liver Protein ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Exercise Induced

Although physical exercise-induced autophagy activation has been considered a therapeutic target to enhance tissue health and extend lifespan, the effects of different exercise models on autophagy in specific metabolic tissues are not completely understood. This descriptive investigation compared the acute effects of endurance (END), exhaustive (ET), strength (ST), and concurrent (CC) physical exercise protocols on markers of autophagy, genes, and proteins in the gastrocnemius muscle, heart, and liver of mice. The animals were euthanized immediately (0 h) and six hours (6 h) after the acute exercise for the measurement of glycogen levels, mRNA expression of Prkaa1, Ppargc1a, Mtor, Ulk1, Becn1, Atg5, Map1lc3b, Sqstm1, and protein levels of Beclin 1 and ATG5. The markers of autophagy were measured by quantifying the protein levels of LC3II and Sqstm1/p62 in response to three consecutive days of intraperitoneal injections of colchicine. In summary, for gastrocnemius muscle samples, the main alterations in mRNA expressions were observed after 6 h and for the ST group, and the markers of autophagy for the CC group were increased (i.e., LC3II and Sqstm1/p62). In the heart, the Beclin 1 and ATG5 levels were downregulated for the ET group. Regarding the markers of autophagy, the Sqstm1/p62 in the heart tissue was upregulated for the END and ST groups, highlighting the beneficial effects of these exercise models. The liver protein levels of ATG5 were downregulated for the ET group. After the colchicine treatment, the liver protein levels of Sqstm1/p62 were decreased for the END and ET groups compared to the CT, ST, and CC groups. These results could be related to diabetes and obesity development or liver dysfunction improvement, demanding further investigations.

scholarly journals Nuclear receptors and AMPK: can exercise mimetics cure diabetes?

2016 ◽  
Vol 57 (1) ◽  
pp. R49-R58 ◽  
Author(s):  
Christopher E Wall ◽  
Ruth T Yu ◽  
Anne R Atkins ◽  
Michael Downes ◽  
Ronald M Evans
Keyword(s):  
Metabolic Syndrome ◽  
Clinical Trials ◽  
Nuclear Receptors ◽  
Metabolic Diseases ◽  
Human Subjects ◽  
Molecular Targets ◽  
Disease Symptoms ◽  
Beneficial Effects ◽  
Increase Energy Expenditure ◽  
Exercise Mimetics

Endurance exercise can lead to systemic improvements in insulin sensitivity and metabolic homeostasis, and is an effective approach to combat metabolic diseases. Pharmacological compounds that recapitulate the beneficial effects of exercise, also known as ‘exercise mimetics’, have the potential to improve disease symptoms of metabolic syndrome. These drugs, which can increase energy expenditure, suppress hepatic gluconeogenesis, and induce insulin sensitization, have accordingly been highly scrutinized for their utility in treating metabolic diseases including diabetes. Nevertheless, the identity of an efficacious exercise mimetic still remains elusive. In this review, we highlight several nuclear receptors and cofactors that are putative molecular targets for exercise mimetics, and review recent studies that provide advancements in our mechanistic understanding of how exercise mimetics exert their beneficial effects. We also discuss evidence from clinical trials using these compounds in human subjects to evaluate their efficacy in treating diabetes.

scholarly journals Importance of mechanical signals in promoting exercise-induced improvements in vasomotor function of aged skeletal muscle resistance arteries

2018 ◽  
Vol 315 (3) ◽  
pp. H602-H609
Author(s):  
Christopher R. Woodman ◽  
John W. Seawright ◽  
Meredith J. Luttrell ◽  
Song Yi Shin ◽  
Andreea Trache
Keyword(s):  
Skeletal Muscle ◽  
Shear Stress ◽  
Short Duration ◽  
Resistance Arteries ◽  
Beneficial Effects ◽  
Vasomotor Function ◽  
Endurance Exercise Training ◽  
Vascular Beds ◽  
Exercise Induced ◽  
Effects Of Aging

Current research indicates that vasomotor responses are altered with aging in skeletal muscle resistance arteries. The changes in vasomotor function are characterized by impaired vasodilator and vasoconstrictor responses. The detrimental effects of aging on vasomotor function are attenuated in some vascular beds after a program of endurance exercise training. The signals associated with exercise responsible for inducing improvements in vasomotor function have been proposed to involve short-duration increases in intraluminal shear stress and/or pressure during individual bouts of exercise. Here, we review evidence that increases in shear stress and pressure, within a range believed to present in these arteries during exercise, promote healthy vasomotor function in aged resistance arteries. We conclude that available research is consistent with the interpretation that short-duration mechanical stimulation, through increases in shear stress and pressure, contributes to the beneficial effects of exercise on vasomotor function in aged skeletal muscle resistance arteries.

Sign in / Sign up

Export Citation Format

Share Document