Exercise-induced irisin release as a determinant of the metabolic response to exercise training in obese youth: the EXIT trial

Obesity is a major risk factor for metabolic disease. Growth differentiation factor 15 (GDF15) has shown promise as a weight loss agent for obesity in animal studies. In healthy lean humans, fasting plasma GDF15 increases after acute exercise. However, the role of GDF15 in human obesity and the response of plasma GDF15 to exercise training in patients with obesity is unknown. Here, 24 sedentary volunteers with obesity [age: 65 ± 1 yr; body mass index (BMI): 35.3 ± 0.9 kg/m2] participated in a supervised 12-wk aerobic exercise intervention: 1 h/day, 5 days/wk at ~85% maximum heart rate with controlled isocaloric diet. As a result, plasma GDF15 was significantly increased (PRE: 644.1 ± 42.6 pg/ml, POST: 704.4 ± 47.2 pg/ml, P < 0.01) after the exercise intervention. Inconsistent with animal models, ΔGDF15 was not correlated with change in weight, BMI, or resting energy expenditure. However, ΔGDF15 was correlated with a reduction in total fat mass ( P < 0.05), abdominal fat mass ( P < 0.05), and android fat mass ( P ≤ 0.05). Participants with a positive GDF15 response to exercise had increased total fat oxidation (PRE: 0.25 ± 0.05 mg·kg−1·min−1, POST: 0.43 ± 0.07 mg·kg−1·min−1, P ≤ 0.05), metabolic flexibility [PRE: −0.01 ± 0.01 delta respiratory quotient (RQ), POST: 0.06 ± 0.01 delta RQ, P < 0.001], and insulin sensitivity (PRE: 0.33 ± 0.01 QUICKI index, POST: 0.34 ± 0.01 QUICKI index, P < 0.01), suggesting a link between GDF15 and fat mass loss as well as exercise-induced metabolic improvement in humans with obesity. We conclude that the exercise-induced increase in plasma GDF15 and the association with reduced fat mass may indicate a role for GDF15 as a therapeutic target for human obesity.

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Experience affects exercise-induced changes in catecholamines, glucose, and FFA

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.1.r169 ◽

1989 ◽

Vol 256 (1) ◽

pp. R169-R173 ◽

Cited By ~ 6

Author(s):

A. J. Scheurink ◽

A. B. Steffens ◽

G. H. Dreteler ◽

L. Benthem ◽

R. Bruntink

Keyword(s):

Metabolic Response ◽

Plasma Catecholamines ◽

Plasma Free Fatty Acid ◽

Blood Component ◽

Experimental Conditions ◽

Glucose Levels ◽

Exercise Induced ◽

Induced Changes ◽

Response To Exercise ◽

First Time

The interference of the experimental conditions on the exercise-induced alterations in plasma catecholamines, plasma free fatty acids, and glucose and insulin concentrations was investigated in rats. Exercise consisted of strenuous swimming against a countercurrent (0.22 m/s) for 15 min in a pool with water of 33 degrees C. Before, during, and after swimming, blood samples were taken through a permanent heart catheter. The blood component levels in rats that were confronted with exercise for the very first time were compared with the levels in rats that were well accustomed to the exercise conditions. The very first time rats swam caused an enhanced release of epinephrine from the adrenal medulla and a reduced output of norepinephrine from the sympathetic nerve endings. Furthermore, in the first time swim group, blood glucose levels were higher and plasma free fatty acid concentrations were lower compared with the well-accustomed animals. There were no differences in plasma insulin concentrations. It is concluded that the experimental conditions may interfere considerably with the hormonal and metabolic response to exercise. Furthermore the results reinforce the idea that the two parts of the sympathoadrenal system are functionally and metabolically dissociated.

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Exercise Training Promotes Sex-Specific Adaptations in Mouse Inguinal White Adipose Tissue

10.2337/figshare.13681663 ◽

2021 ◽

Author(s):

Pasquale Nigro ◽

Roeland J. W. Middelbeek ◽

Christiano R. R. Alves ◽

Susana Rovira–Llopis ◽

Krithika Ramachandran ◽

...

Keyword(s):

Adipose Tissue ◽

Exercise Training ◽

White Adipose Tissue ◽

Metabolic Response ◽

Wheel Running ◽

Secretory Protein ◽

Acid Uptake ◽

Male Mice ◽

Female Mice ◽

Response To Exercise

Recent studies demonstrate that adaptations to white adipose tissue are important components of the beneficial effects of exercise training on metabolic health. Exercise training favorably alters the phenotype of subcutaneous inguinal white adipose tissue (iWAT) in male mice including decreasing fat mass, improving mitochondrial function, inducing beiging and stimulating the secretion of adipokines. Here, we find that despite performing more voluntary wheel running compared to males, these adaptations do not occur in the iWAT of female mice. Consistent with sex-specific adaptations, we report that mRNA expression of androgen receptor co-activators are upregulated in iWAT from trained male mice, and that testosterone treatment of primary adipocytes derived from the iWAT of male, but not female mice, phenocopies exercise-induced metabolic adaptations. Sex-specificity also occurs in the secretome profile, as we identify Cysteine Rich Secretory Protein 1(Crisp1) as a novel adipokine that is only secreted from male iWAT in response to exercise. Crisp1 expression is upregulated by testosterone and functions to increase glucose and fatty acid uptake. Our finding that adaptations to iWAT with exercise training are dramatically greater in male mice has potential clinical implications for understanding the different metabolic response to exercise training in males and females, and demonstrates the importance of investigating both sexes in studies of adipose tissue biology.

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Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Cells ◽

10.3390/cells10123306 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3306

Author(s):

Weiwei Zhu ◽

Namood E Sahar ◽

Hafiz Muhammad Ahmad Javaid ◽

Eun Seon Pak ◽

Guang Liang ◽

...

Keyword(s):

Exercise Training ◽

Clinical Problem ◽

Underlying Mechanism ◽

Competitive Binding ◽

Alcoholic Fatty Liver ◽

Exercise Induced ◽

Response To Exercise ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise is considered to improve NAFLD but the underlying mechanism is still unclear. In this study, we examined the protective effect and molecular mechanism of exercise on high-fat diet (HFD)-induced liver injury. In an HFD-induced NAFLD mouse model, exercise training significantly decreased hepatic steatosis and fibrosis. Interestingly, exercise training blocked the binding of MD2-TLR4 and decreased the downstream inflammatory response. Irisin is a myokine that is highly expressed in response to exercise and exerts anti-inflammatory effects. We found that circulating irisin levels and muscle irisin expression were significantly increased in exercised mice, suggesting that irisin could mediate the effect of exercise on NAFLD. In vitro studies showed that irisin improved lipid metabolism, fibrosis, and inflammation in palmitic acid (PA)-stimulated AML12 cells. Moreover, binding assay results showed that irisin disturbed MD2-TLR4 complex formation by directly binding with MD2 but not TLR4, and interfered with the recognition of stimuli such as PA and lipopolysaccharide with MD2. Our study provides novel evidence that exercise-induced irisin inhibits inflammation via competitive binding with MD2 to improve NAFLD. Thus, irisin could be considered a potential therapy for NAFLD.

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The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake

European Journal of Clinical Nutrition ◽

10.1038/ejcn.2013.277 ◽

2014 ◽

Vol 68 (5) ◽

pp. 581-586 ◽

Cited By ~ 30

Author(s):

M Hopkins ◽

C Gibbons ◽

P Caudwell ◽

P M Hellström ◽

E Näslund ◽

...

Keyword(s):

Weight Loss ◽

Energy Expenditure ◽

Energy Intake ◽

Metabolic Response ◽

Exercise Induced ◽

Response To Exercise

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Effect of hydration state on resistance exercise-induced endocrine markers of anabolism, catabolism, and metabolism

Journal of Applied Physiology ◽

10.1152/japplphysiol.01010.2007 ◽

2008 ◽

Vol 105 (3) ◽

pp. 816-824 ◽

Cited By ~ 59

Author(s):

Daniel A. Judelson ◽

Carl M. Maresh ◽

Linda M. Yamamoto ◽

Mark J. Farrell ◽

Lawrence E. Armstrong ◽

...

Keyword(s):

Resistance Exercise ◽

Body Mass ◽

Metabolic Response ◽

Hydration Status ◽

Training Adaptations ◽

Carbohydrate And Lipid Metabolism ◽

Hydration State ◽

Total Body ◽

Exercise Induced ◽

Response To Exercise

Hypohydration (decreased total body water) exacerbates the catabolic hormonal response to endurance exercise with unclear effects on anabolic hormones. Limited research exists that evaluates the effect of hypohydration on endocrine responses to resistance exercise; this work merits attention as the acute postexercise hormonal environment potently modulates resistance training adaptations. The purpose of this study was to examine the effect of hydration state on the endocrine and metabolic responses to resistance exercise. Seven healthy resistance-trained men (age = 23 ± 4 yr, body mass = 87.8 ± 6.8 kg, body fat = 11.5 ± 5.2%) completed three identical resistance exercise bouts in different hydration states: euhydrated (EU), hypohydrated by ∼2.5% body mass (HY25), and hypohydrated by ∼5.0% body mass (HY50). Investigators manipulated hydration status via controlled water deprivation and exercise-heat stress. Cortisol, epinephrine, norepinephrine, testosterone, growth hormone, insulin-like growth factor-I, insulin, glucose, lactate, glycerol, and free fatty acids were measured during euhydrated rest, immediately preceding resistance exercise, immediately postexercise, and during 60 min of recovery. Body mass decreased 0.2 ± 0.4, 2.4 ± 0.4, and 4.8 ± 0.4% during EU, HY25, and HY50, respectively, supported by humoral and urinary changes that clearly indicated subjects achieved three distinct hydration states. Hypohydration significantly 1) increased circulating concentrations of cortisol and norepinephrine, 2) attenuated the testosterone response to exercise, and 3) altered carbohydrate and lipid metabolism. These results suggest that hypohydration can modify the hormonal and metabolic response to resistance exercise, influencing the postexercise circulatory milieu.

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Exercise-induced expression of VEGF and salvation of myocardium in the early stage of myocardial infarction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01393.2007 ◽

2009 ◽

Vol 296 (2) ◽

pp. H389-H395 ◽

Cited By ~ 30

Author(s):

Guifu Wu ◽

Jamal S. Rana ◽

Joanna Wykrzykowska ◽

Zhimin Du ◽

Qingen Ke ◽

...

Keyword(s):

Exercise Training ◽

Exercise Group ◽

Angiogenic Factors ◽

Vegf Expression ◽

Infarcted Myocardium ◽

Sedentary Group ◽

Exercise Preconditioning ◽

Exercise Induced ◽

Response To Exercise ◽

The Impact

The mechanism of exercise-induced benefit and angiogenesis in ischemic heart disease remains poorly defined. This study was designed to investigate the effects of exercise training on the expression of angiogenic factors and angiogenesis in the infarcted myocardium [myocarial infaction (MI)]. Sixty-three male FVB mice were used for study and were divided into subgroups to test the response to exercise: the time-dependent expression of angiogenic factors to exercise training in normal ( group 1; n = 12) and infarcted myocardium ( group 2; n = 15) and the exercise-induced angiogenic response in normal and infarcted myocardium ( group 3; n = 20) as well as the impact of exercise preconditioning on infarcted myocardium ( group 4; n = 26). Exercise training consisted of daily treadmill exercise for 1 h for 3 days. Expression of VEGF and its receptors Flt-1 and Flk-1 was upregulated by exercise training in mice with MI. Exercise-induced VEGF expression in the MI group was higher than that in the sham (control) group. Cell proliferation assessment showed a significantly higher ( P < 0.05) number of bromodeoxyuridine-positive cells in post-MI mice in the exercise group as opposed to post-MI mice in the sedentary group. 2,3,5-Triphenyltetrazolium chloride staining revealed a profound difference in the size of MI (18.25 ± 2.93%) in the exercise group versus the sedentary group (29.26 ± 7.64%, P = 0.02). Moreover, exercise preconditioning before MI promoted VEGF expression at both mRNA and protein levels. In conclusion, activation of VEGF and its receptors occurs in the infarcted mice heart in response to exercise, which results in decreased infarct size and improved angiogenesis.

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MyoView: Fully-automated image segmentation method to analyse skeletal muscle cross section in exercise-induced regenerating myofibers

10.1101/2021.08.24.457394 ◽

2021 ◽

Author(s):

Masoud Rahmati ◽

Abdolreza Rashno

Keyword(s):

Skeletal Muscle ◽

Image Segmentation ◽

Exercise Training ◽

Cross Section ◽

Neutrosophic Set ◽

Fiber Types ◽

Segmentation Method ◽

Post Exercise ◽

Exercise Induced ◽

Response To Exercise

AbstractSkeletal muscle is an adaptive tissue with the ability to regenerate in response to exercise training. Cross-sectional area (CSA) quantification, as a main parameter to assess muscle regeneration capability, is highly tedious and time-consuming, necessitating an accurate and automated approach to analysis. Although several excellent programs are available to automate analysis of muscle histology, they fail to efficiently and accurately measure CSA in regenerating myofibers in response to exercise training. Here, we have developed a novel fully-automated image segmentation method based on neutrosophic set algorithms to analyse whole skeletal muscle cross sections in exercise-induced regenerating myofibers, referred as MyoView, designed to obtain accurate fiber size and distribution measurements. MyoView provides relatively efficient, accurate, and reliable measurements for detecting different myofibers and CSA quantification in response to the post-exercise regenerating process. We showed that MyoView is comparable with manual quantification. We also showed that MyoView is more accurate and efficient to measure CSA in post-exercise regenerating myofibers as compared with Open-CSAM, MuscleJ, SMASH and MyoVision. Furthermore, we demonstrated that to obtain an accurate CSA quantification of exercise-induced regenerating myofibers, whole muscle cross-section analysis is an essential part, especially for the measurement of different fiber-types. We present MyoView as a new tool for CSA quantification in skeletal muscle from any experimental condition including exercise-induced regenerating myofibers.

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Immunometabolism: A Multi-Omics Approach to Interpreting the Influence of Exercise and Diet on the Immune System

Annual Review of Food Science and Technology ◽

10.1146/annurev-food-032818-121316 ◽

2019 ◽

Vol 10 (1) ◽

pp. 341-363 ◽

Cited By ~ 11

Author(s):

David C. Nieman ◽

Mary Ann Lila ◽

Nicholas D. Gillitt

Keyword(s):

Metabolic Response ◽

Immune Dysfunction ◽

Data Sets ◽

Dietary Interventions ◽

Cell Level ◽

Carbohydrate Ingestion ◽

Metabolic Recovery ◽

Exercise Induced ◽

Scientific Endeavor ◽

Response To Exercise

Immunometabolism is an evolving field of scientific endeavor that merges immunology and metabolism and has provided valuable context when evaluating the influence of dietary interventions on exercise-induced immune dysfunction. Metabolomics, lipidomics, and proteomics provide a system-wide view of the metabolic response to exercise by simultaneously measuring and identifying a large number of small-molecule metabolites, lipids, and proteins. Many of these are involved with immune function and regulation and are sensitive to dietary influences, especially acute carbohydrate ingestion from either sugar beverages or fruits such as bananas. Emerging evidence using large multi-omics data sets supports the combined intake of fruit sugars and phytochemicals by athletes during heavy exertion as an effective strategy to improve metabolic recovery, augment viral defense, and counter postexercise inflammation and immune dysfunction at the cell level. Multi-omics methodologies have given investigators new outcome targets to assess the efficacy of various dietary interventions for physiologically stressed athletes.

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Exercise Training Promotes Sex-Specific Adaptations in Mouse Inguinal White Adipose Tissue

10.2337/figshare.13681663.v1 ◽

2021 ◽

Author(s):

Pasquale Nigro ◽

Roeland J. W. Middelbeek ◽

Christiano R. R. Alves ◽

Susana Rovira–Llopis ◽

Krithika Ramachandran ◽

...

Keyword(s):

Adipose Tissue ◽

Exercise Training ◽

White Adipose Tissue ◽

Metabolic Response ◽

Wheel Running ◽

Secretory Protein ◽

Acid Uptake ◽

Male Mice ◽

Female Mice ◽

Response To Exercise

Recent studies demonstrate that adaptations to white adipose tissue are important components of the beneficial effects of exercise training on metabolic health. Exercise training favorably alters the phenotype of subcutaneous inguinal white adipose tissue (iWAT) in male mice including decreasing fat mass, improving mitochondrial function, inducing beiging and stimulating the secretion of adipokines. Here, we find that despite performing more voluntary wheel running compared to males, these adaptations do not occur in the iWAT of female mice. Consistent with sex-specific adaptations, we report that mRNA expression of androgen receptor co-activators are upregulated in iWAT from trained male mice, and that testosterone treatment of primary adipocytes derived from the iWAT of male, but not female mice, phenocopies exercise-induced metabolic adaptations. Sex-specificity also occurs in the secretome profile, as we identify Cysteine Rich Secretory Protein 1(Crisp1) as a novel adipokine that is only secreted from male iWAT in response to exercise. Crisp1 expression is upregulated by testosterone and functions to increase glucose and fatty acid uptake. Our finding that adaptations to iWAT with exercise training are dramatically greater in male mice has potential clinical implications for understanding the different metabolic response to exercise training in males and females, and demonstrates the importance of investigating both sexes in studies of adipose tissue biology.

Download Full-text