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The Impact of Endurance Exercise Intensity on Local and Systemic Hormonal and Cytokine Responses in the Recreationally Active Young and Old

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The Impact of Endurance Exercise Intensity on Local and Systemic Hormonal and Cytokine Responses in the Recreationally Active Young and Old The impact of endurance exercise intensity on local and systemic hormonal and cytokine responses in the recreationally active young and old Andrew David Moss A thesis submitted in partial fulfillment of the requirements of the Manchester Metropolitan University for the degree of Doctor of Philosophy Faculty of Science and Engineering PhD 2015 Abstract Propelled by the significant socio-economic issues presented by obesity and an ageing population, research has identified links between physical activity, metabolism and disease, and quality of life. Our overall aim was to implement an empirically informed, palatable acute endurance exercise intervention that elicits beneficial hormonal responses with the potential for improved health/quality of life across the lifespan. Two groups of similar male participants (Study 1: n = 6; age, 28 ± 5 yrs.; BMI, 25 ± 4 kg/m2 - Study 2: n = 7; age, 26 ± 7 yrs.; BMI, 25 ± 4 kg/m2) performed equal work (varying duration) moderate (80 % GET) (M) and heavy (30 % ) (H) (Study 1), and H and very heavy (60 % ) (VH) (Study 2) acute constant work-load cycle ergometer exercise trials, respectively (Chapter 3). Analysis of bioptic material indicated increased mRNA (GAPDH normalised) in skeletal muscle for IL-6: baseline (B) vs. M (P = 0.006), H (P < 0.001) and VH (P < 0.001), and M vs. VH (P = 0.02); TNFα: B vs. VH (P = 0.04) and SOCS3 B vs. M (P = 0.02) and VH (P = 0.04). Exercise was without effect in subcutaneous adipose tissue (Chapter 4). The systemic concentrations of IL-6 increased and remained elevated for 24 hrs. in response to exercise. The increase was greatest following M (P = 0.001). IGF-I and cortisol concentrations declined by 60 min post- exercise (P = 0.001 and P = 0.04, respectively) (M, H and VH). GH increased to peak at the end of exercise (P < 0.001) (M, H and VH) (Chapter 5). To investigate the effect of age, groups of male participants (Study 3: 20 - 30 yrs., n = 8; 30 - 40 yrs., n = 10; 40 - 50 yrs., n = 8; 50 - 60 yrs., n = 8) performed a similar 30 min bout of heavy (30 % ) domain exercise (Chapter 6). The systemic concentrations of IL-6 displayed a bi-phasic profile in all groups. IL-6 increased during exercise at 10 min and then 60 min post-exercise (P < 0.001). Insulin and leptin declined during exercise in all groups (P < 0.001 and P = 0.002, respectively). Adiponectin was unchanged. GH increased similarly in all groups to peak again at the end of exercise (P < 0.001). IGF-I was unchanged. Concentrations were consistently higher in the 20 – 30 group however (P = 0.001). Cortisol declined similarly post-exercise in all groups (P < 0.001). We suggest that the oxygen uptake dynamics approach used here should be used when investigating physiological phenomenon potentially sensitive to skeletal muscle metabolic threshold events. We conclude that the exercise-induced hormone and cytokine responses studied in recreationally active health males between 20 and 60 yrs. age most likely reflects the requirements of metabolism. Further work should assess the effectiveness of this modified approach against resistance exercise in a training study format. ii Acknowledgements If it is true that something easily acquired is not really worth having then right now I feel that this document is probably one of the most valuable items I possess. The ‘journey’ has been long and hard, but ultimately rewarding. I would like to express my sincere gratitude to the following: Professor Claire Stewart, original Director of Studies, for her friendship, patience and confidence in me when I doubted myself throughout this programme of study. Dr Hans Degens for allowing me to continue with my studies by taking over the role of Director of Studies, keeping the banner high and Dutch humour. Professor Jörn Rittweger MD for making it possible to obtain the skeletal muscle and adipose tissue biopsies, and German humour. Doctor Nasser Al-Shanti and Professor David Jones for valuable contributions to the learning and research process. Drs Liz and Lucy for kind and encouraging words, listening, and providing opportunities to de-stress, oh and Gin! Professor Emeritus Les Burwitz, Mark McDonagh and Hilary Legge in establishing support for the programme of study initially, and Professors Neil Fowler and Paul Holmes, and Doctors Adrian Burden and Nick Smith for continued friendship and support. I would like to thank my technical and support staff colleagues for constantly asking “How are you getting on with your PhD” and “When are you going to finish your PhD”. Lastly, I would like to express sincere thanks to David Tomlinson for his considerable effort, without which I would not have been able to complete the feasibility studies, and all of the participants who freely gave their time, blood, sweat and other small parts of themselves. iii Authors declaration I declare that the work in this thesis was carried out in accordance with the regulations of Manchester Metropolitan University. Apart from the help and advice acknowledged, the work within was solely completed and carried out by the author. Any views expressed in this thesis are those of the author and in no way represent those of Manchester Metropolitan University. This thesis has not been presented to any other university for examination either in the United Kingdom or overseas. No portion of the work referred to in this research project has been submitted in support of an application for another degree or qualification of this or any other university or institute of learning. Copyright in text of this research project rests with the author. The ownership of any intellectual property rights which maybe described in this research project is vested in Manchester Metropolitan University and may not be made available for use to any third parties without the written permission of Manchester Metropolitan University. Signed:……………………………………… Dated: ……25th February 2015…………… iv Dedication Dear Amy, 2015 is going to be a wonderful year. v Publications and presentations IRM Symposium Presentation: Stewart, C. E., Saini, A., Sharples, A. P., Moss, A. D., Dimchev, G., Durcan, P., Faulkner, S. H., and Al-Shanti, N. (2010). The Interaction of Growth Factors and Cytokines in the Regulation of Muscle Growth and Atrophy. vi Contents Chapter Heading Page Title page i Abstract ii Acknowledgements iii Authors declaration iv Dedication v Publications and presentations vi Contents vii Glossary of abbreviations xiv List of tables xxi List of figures xxii Chapter 1. Literature review 26 1.1. Age-related skeletal muscle functional decline 26 1.1.1. The ageing process: hormone and cytokine adaptations 27 1.1.2. The relationship between Inflammation, inflammageing and 29 increasing adipose tissue mass 1.2. Exercise as a therapeutic intervention 30 1.2.1. Skeletal muscle derived ‘myokine’ interactions 32 1.2.2. Adipose tissue derived ‘adipokine’ interactions 34 1.2.3. The influence of endurance exercise on systemic protein 39 abundance 1.2.3.1. Insulin 40 1.2.3.2. Insulin-like growth factor-I 42 1.2.3.3. Growth hormone 44 1.2.3.4. Cortisol 45 1.3. Overall aim, goal and chapter objectives 48 Chapter 2. General methods 49 2.1. Laboratory 49 vii 2.1.1. Health and safety 49 2.1.2. Environmental conditions 49 2.2. Participants 50 2.2.1. Ethical approval 50 2.2.2. Participant recruitment 50 2.2.2.1. Exclusion criteria 50 2.2.3. Initial measurements: body mass, stature and body mass index 51 2.2.4. Participant preparation 51 2.3. Electronically-braked cycle ergometry 51 2.3.1. Maximal oxygen uptake determination protocol 52 2.3.1.1. Methodological considerations: maximal incremental exercise 52 testing ˙ 2.3.2. Criteria for a successful V O2max test 52 2.3.2.1. Methodological considerations: criteria for a successful max 53 test 2.4. Heart rate monitoring 54 2.5. Expired gas sampling 54 2.5.1. Methodological considerations: an oxygen uptake dynamics 54 approach ˙ 2.5.1.1. The V O2 response to constant work-load exercise 54 2.5.1.2. The gas exchange threshold 56 2.5.1.3. Maximal lactate steady state 56 2.5.1.4. The concept of exercise domains 56 2.5.1.5. Determination of exercise trial intensity from raw pulmonary gas 59 exchange data 2.5.1.6. Explanation and justification for exercise trial intensities 61 2.5.1.7. Example of calculations to determine exercise trial duration 62 according to equal work done 2.5.1.8. Exercise trial protocols 62 2.5.1.8.1. Overview of exercise studies 63 2.6. Blood sampling 68 2.6.1. Venous blood sampling 68 2.6.2. Capillary blood sampling 68 2.6.2.1. Blood lactate 68 2.6.2.2. Blood glucose 69 viii 2.6.3. Enzyme-linked immunosorbent assay analyses 70 2.7. Skeletal muscle and subcutaneous adipose tissue sampling 71 2.7.1. Skeletal muscle and subcutaneous adipose biopsy procedure 71 2.7.2. Skeletal muscle and adipose tissue homogenisation 72 2.7.3. Ribonucleic acid isolation 73 2.7.4. Oligonucleotide primer design and synthesis 73 2.7.5. Reverse transcription-polymerase chain reaction method and data 75 analysis 2.8. Statistical analyses 77 Chapter 3. Maximal incremental exercise vs. acute ‘domain-based’ 78 constant work-load cycle ergometry: comparison of cardio-respiratory responses 3.1. Abstract 78 3.2. Introduction 79 3.3. Methods 80 3.3.1 Study design 80 3.3.2. Participants [2.2.] 81 3.3.3. Maximal oxygen uptake determination protocol [2.3.1.] 81 3.3.4. Determination of exercise trial intensity and duration 81 [2.5.1.5.
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