Exercise-Induced Alterations in Skeletal Muscle, Heart, Liver, and Serum Metabolome Identified by Non-Targeted Metabolomics Analysis

Exercise training improves glucose homeostasis through enhanced insulin sensitivity in skeletal muscle. Muscle contraction through physical exercise is a physiological stimulus that elicits multiple biochemical and biophysical responses and therefore requires an appropriate control network. Mitogen-activated protein kinase (MAPK) signalling pathways constitute a network of phosphorylation cascades that link cellular stress to changes in transcriptional activity. MAPK cascades are divided into four major subfamilies, including extracellular signal-regulated kinases 1 and 2, p38 MAPK, c-Jun NH2-terminal kinase and extracellular signal-regulated kinase 5. The present review will present the current understanding of parallel MAPK signalling in human skeletal muscle in response to exercise and muscle contraction, with an emphasis on identifying potential signalling mechanisms responsible for changes in gene expression.

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Exercise, heat shock proteins and insulin resistance

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0529 ◽

2017 ◽

Vol 373 (1738) ◽

pp. 20160529 ◽

Cited By ~ 19

Author(s):

Ashley E. Archer ◽

Alex T. Von Schulze ◽

Paige C. Geiger

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Proteins ◽

Metabolic Effects ◽

Diabetic Patients ◽

Alcoholic Fatty Liver ◽

Insulin Resistant ◽

Exercise Induced ◽

Shock Proteins

Best known as chaperones, heat shock proteins (HSPs) also have roles in cell signalling and regulation of metabolism. Rodent studies demonstrate that heat treatment, transgenic overexpression and pharmacological induction of HSP72 prevent high-fat diet-induced glucose intolerance and skeletal muscle insulin resistance. Overexpression of skeletal muscle HSP72 in mice has been shown to increase endurance running capacity nearly twofold and increase mitochondrial content by 50%. A positive correlation between HSP72 mRNA expression and mitochondrial enzyme activity has been observed in human skeletal muscle, and HSP72 expression is markedly decreased in skeletal muscle of insulin resistant and type 2 diabetic patients. In addition, decreased levels of HSP72 correlate with insulin resistance and non-alcoholic fatty liver disease progression in livers from obese patients. These data suggest the targeted induction of HSPs could be a therapeutic approach for preventing metabolic disease by maintaining the body's natural stress response. Exercise elicits a number of metabolic adaptations and is a powerful tool in the prevention and treatment of insulin resistance. Exercise training is also a stimulus for increased HSP expression. Although the underlying mechanism(s) for exercise-induced HSP expression are currently unknown, the HSP response may be critical for the beneficial metabolic effects of exercise. Exercise-induced extracellular HSP release may also contribute to metabolic homeostasis by actively restoring HSP72 content in insulin resistant tissues containing low endogenous levels of HSPs. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

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Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2013.10.005 ◽

2013 ◽

Vol 441 (1) ◽

pp. 36-41 ◽

Cited By ~ 22

Author(s):

Shin-ichi Ikeda ◽

Yoshifumi Tamura ◽

Saori Kakehi ◽

Kageumi Takeno ◽

Minako Kawaguchi ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Mouse Skeletal Muscle ◽

Exercise Induced

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MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

Nature Communications ◽

10.1038/s41467-020-20790-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Joseph C. Reynolds ◽

Rochelle W. Lai ◽

Jonathan S. T. Woodhead ◽

James H. Joly ◽

Cameron J. Mitchell ◽

...

Keyword(s):

Skeletal Muscle ◽

Healthy Aging ◽

Metabolic Stress ◽

Muscle Metabolism ◽

Physical Capacity ◽

Physical Decline ◽

Age Dependent ◽

Exercise Induced ◽

Muscle Homeostasis ◽

Metabolic Fitness

AbstractHealthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.

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Exercise-induced Protein Arginine Methyltransferase Expression in Skeletal Muscle

Medicine & Science in Sports & Exercise ◽

10.1249/mss.0000000000001476 ◽

2018 ◽

Vol 50 (3) ◽

pp. 447-457 ◽

Cited By ~ 6

Author(s):

TIFFANY L. VANLIESHOUT ◽

DEREK W. STOUTH ◽

TANIA TAJIK ◽

VLADIMIR LJUBICIC

Keyword(s):

Skeletal Muscle ◽

Protein Arginine Methyltransferase ◽

Arginine Methyltransferase ◽

Exercise Induced

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

Proceedings of The Nutrition Society ◽

10.1079/pns2004353 ◽

2004 ◽

Vol 63 (2) ◽

pp. 189-197 ◽

Cited By ~ 3

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.

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