Effects of Exercise to Improve Cardiovascular Health

Obesity is a complex disease that affects whole body metabolism and is associated with an increased risk of cardiovascular disease (CVD) and Type 2 diabetes (T2D). Physical exercise results in numerous health benefits and is an important tool to combat obesity and its co-morbidities, including cardiovascular disease. Exercise prevents both the onset and development of cardiovascular disease and is an important therapeutic tool to improve outcomes for patients with cardiovascular disease. Some benefits of exercise include enhanced mitochondrial function, restoration and improvement of vasculature, and the release of myokines from skeletal muscle that preserve or augment cardiovascular function. In this review we will discuss the mechanisms through which exercise promotes cardiovascular health.

[1]  H. Ellingsgaard,et al.  Increased Number of Islet-Associated Macrophages in Type 2 Diabetes , 2007, Diabetes.

[2]  B. Pedersen,et al.  AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise. , 2004, Biochemical and biophysical research communications.

[3]  A. Wende,et al.  My Sweetheart Is Broken: Role of Glucose in Diabetic Cardiomyopathy , 2016, Diabetes & metabolism journal.

[4]  T. Murohara,et al.  C1q/TNF‐related protein‐1 functions to protect against acute ischemic injury in the heart , 2016, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[5]  H. Sabbah,et al.  Animal models of insulin resistance and heart failure , 2013, Heart Failure Reviews.

[6]  C. Ballantyne,et al.  Skeletal muscle inflammation and insulin resistance in obesity , 2017, The Journal of clinical investigation.

[7]  N. Smart,et al.  Effect of exercise training on endothelial function in heart failure patients: A systematic review meta-analysis. , 2017, International journal of cardiology.

[8]  D. Kitzman,et al.  Sarcopenic Obesity and the Pathogenesis of Exercise Intolerance in Heart Failure with Preserved Ejection Fraction , 2015, Current Heart Failure Reports.

[9]  S. Powers,et al.  Exercise protects cardiac mitochondria against ischemia-reperfusion injury. , 2012, Medicine & Science in Sports & Exercise.

[10]  M. Nikolaidis,et al.  Effect of exercise training on the fatty acid composition of lipid classes in rat liver, skeletal muscle, and adipose tissue , 2005, European Journal of Applied Physiology.

[11]  H. T. Yang,et al.  What makes vessels grow with exercise training? , 2004, Journal of applied physiology.

[12]  B. Klop,et al.  Dyslipidemia in Obesity: Mechanisms and Potential Targets , 2013, Nutrients.

[13]  Peter Libby,et al.  Inflammation and cardiovascular disease mechanisms. , 2006, The American journal of clinical nutrition.

[14]  P. Poirier,et al.  The Impact of Burst Exercise on Cardiometabolic Status of Patients Newly Diagnosed With Type 2 Diabetes. , 2017, The Canadian journal of cardiology.

[15]  M. Febbraio,et al.  Muscle as an endocrine organ: focus on muscle-derived interleukin-6. , 2008, Physiological reviews.

[16]  H Roskamm,et al.  Effects of short-term exercise training and activity restriction on functional capacity in patients with severe chronic congestive heart failure. , 1996, The American journal of cardiology.

[17]  V. Vieira,et al.  Effects of exercise and low-fat diet on adipose tissue inflammation and metabolic complications in obese mice. , 2009, American journal of physiology. Endocrinology and metabolism.

[18]  I-Min Lee,et al.  Dose Response Between Physical Activity and Risk of Coronary Heart Disease: A Meta-Analysis , 2011, Circulation.

[19]  Martin R. Lindley,et al.  The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease , 2011, Nature Reviews Immunology.

[20]  R. Rugulies,et al.  Overweight, obesity, and risk of cardiometabolic multimorbidity: pooled analysis of individual-level data for 120 813 adults from 16 cohort studies from the USA and Europe , 2017, The Lancet. Public health.

[21]  Heinrich Taegtmeyer,et al.  Rethinking cardiac metabolism: metabolic cycles to refuel and rebuild the failing heart , 2014, F1000prime reports.

[22]  J. Buckley,et al.  Health benefits of a 4-month group-based diet and lifestyle modification program for individuals with metabolic syndrome. , 2009, Obesity research & clinical practice.

[23]  G. Ronzitti,et al.  Emerging Issues in AAV-Mediated In Vivo Gene Therapy , 2017, Molecular therapy. Methods & clinical development.

[24]  Y. Ohashi,et al.  Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis. , 2007, Archives of internal medicine.

[25]  S. Shoelson,et al.  Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB , 2005, Nature Medicine.

[26]  D. Seals,et al.  Exercise Protects Against Myocardial Ischemia–Reperfusion Injury via Stimulation of &bgr;3-Adrenergic Receptors and Increased Nitric Oxide Signaling: Role of Nitrite and Nitrosothiols , 2011, Circulation research.

[27]  F. Rengo,et al.  Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart. , 2008, Cardiovascular research.

[28]  T. Rabelink,et al.  Free radical production by dysfunctional eNOS , 2004, Heart.

[29]  W. Kraus,et al.  Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial. , 2009, JAMA.

[30]  R. Re Obesity-related hypertension. , 2009, The Ochsner journal.

[31]  T. Wadden,et al.  Benefits of Modest Weight Loss in Improving Cardiovascular Risk Factors in Overweight and Obese Individuals With Type 2 Diabetes , 2011, Diabetes Care.

[32]  David R Thompson,et al.  Exercise-based cardiac rehabilitation for coronary heart disease. , 2016, The Cochrane database of systematic reviews.

[33]  H. Fiddler,et al.  The Physiotherapist's Pocket Guide to Exercise: Assessment, Prescription and Training , 2009 .

[34]  Claude Bouchard,et al.  Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits. , 2015, Cell metabolism.

[35]  L. Goodyear,et al.  Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle. , 2014, Advances in physiology education.

[36]  Rossella D'Oria,et al.  Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. , 2018, Vascular pharmacology.

[37]  Bente Klarlund Pedersen,et al.  Muscles and their myokines , 2011, Journal of Experimental Biology.

[38]  C. Fox,et al.  Pericardial Fat is Associated With Atrial Conduction: The Framingham Heart Study , 2014, Journal of the American Heart Association.

[39]  R. Jacobs,et al.  Adaptations of skeletal muscle mitochondria to exercise training , 2016, Experimental physiology.

[40]  Robert Ross,et al.  Reduction in Obesity and Related Comorbid Conditions after Diet-Induced Weight Loss or Exercise-Induced Weight Loss in Men , 2000, Annals of Internal Medicine.

[41]  Ping Chen,et al.  Exercise Training Protects Against Acute Myocardial Infarction via Improving Myocardial Energy Metabolism and Mitochondrial Biogenesis , 2015, Cellular Physiology and Biochemistry.

[42]  J. Hilden,et al.  High-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide in patients with stable coronary artery disease: a prognostic study within the CLARICOR Trial , 2011, Scandinavian journal of clinical and laboratory investigation.

[43]  B. Pedersen,et al.  Role of myokines in exercise and metabolism. , 2007, Journal of applied physiology.

[44]  R. V. van Dam,et al.  Long‐term effectiveness of diet‐plus‐exercise interventions vs. diet‐only interventions for weight loss: a meta‐analysis , 2009, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[45]  Shu-zhong Jiang,et al.  Obesity and hypertension , 2016, Experimental and therapeutic medicine.

[46]  S. Coppack,et al.  Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone , 2005, Circulation.

[47]  C. Fischer Interleukin-6 in acute exercise and training: what is the biological relevance? , 2006, Exercise immunology review.

[48]  E. Olson,et al.  Muscle as a "mediator" of systemic metabolism. , 2015, Cell metabolism.

[49]  Dong Li,et al.  The Effects of Exercise on Cardiovascular Biomarkers: New Insights, Recent Data, and Applications. , 2017, Advances in experimental medicine and biology.

[50]  K. Donato,et al.  Body mass index and the prevalence of hypertension and dyslipidemia. , 2000, Obesity research.

[51]  T. Murohara,et al.  Myonectin Is an Exercise-Induced Myokine That Protects the Heart From Ischemia-Reperfusion Injury , 2018, Circulation research.

[52]  J. Borges,et al.  Cardiac Ischemia/Reperfusion Injury: The Beneficial Effects of Exercise. , 2017, Advances in experimental medicine and biology.

[53]  E. Abel,et al.  Insulin resistance: metabolic mechanisms and consequences in the heart. , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[54]  Ganesh V. Halade,et al.  Obesity and Cardiometabolic Defects in Heart Failure Pathology. , 2017, Comprehensive Physiology.

[55]  P. Thompson,et al.  The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. , 2005, Journal of the American College of Cardiology.

[56]  S. Powers,et al.  Sugar or fat: The metabolic choice of the trained heart. , 2018, Metabolism: clinical and experimental.

[57]  G. Schuler,et al.  Effect of exercise on coronary endothelial function in patients with coronary artery disease. , 2000, The New England journal of medicine.

[58]  Richelle J. Koopman,et al.  Insulin Sensitivity Following Exercise Interventions , 2014, Journal of primary care & community health.

[59]  C. Block,et al.  Mechanisms linking obesity with cardiovascular disease , 2006, Nature.

[60]  B. K. Pedersen The diseasome of physical inactivity – and the role of myokines in muscle–fat cross talk , 2009, The Journal of physiology.

[61]  I. Piña,et al.  Exercise and heart failure: A statement from the American Heart Association Committee on exercise, rehabilitation, and prevention. , 2003, Circulation.

[62]  R. Lerch,et al.  Postinfarction heart failure in rats is associated with upregulation of GLUT-1 and downregulation of genes of fatty acid metabolism. , 2001, Cardiovascular research.

[63]  Rick B. Vega,et al.  Molecular Mechanisms Underlying Cardiac Adaptation to Exercise. , 2017, Cell metabolism.

[64]  G. Aurigemma,et al.  Cardiac remodeling in obesity. , 2013, Circulation. Cardiovascular imaging.

[65]  C. Wolff,et al.  Markers of human skeletal muscle mitochondrial biogenesis and quality control: effects of age and aerobic exercise training. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[66]  J. Hawley,et al.  Integrative Biology of Exercise , 2014, Cell.

[67]  H. Taegtmeyer,et al.  Adaptation and Maladaptation of the Heart in Diabetes: Part II: Potential Mechanisms , 2002, Circulation.

[68]  S. Blair,et al.  The effect of different doses of aerobic exercise training on endothelial function in postmenopausal women with elevated blood pressure: results from the DREW study , 2011, British Journal of Sports Medicine.

[69]  Tommy Boone,et al.  Introduction to Exercise Physiology , 2013 .

[70]  S. Headley,et al.  The Effects of Chronic Aerobic Exercise on Cardiovascular Risk Factors in Persons with Diabetes Mellitus , 2017, Current Diabetes Reports.

[71]  G. Lopaschuk,et al.  Cardiac Energy Metabolism in Obesity , 2007, Circulation research.

[72]  Chiew Y Wong,et al.  Clinical Utility of Exercise Training in Heart Failure with Reduced and Preserved Ejection Fraction , 2015, Clinical Medicine Insights. Cardiology.

[73]  B. Kundu,et al.  Quantitative PET Imaging Detects Early Metabolic Remodeling in a Mouse Model of Pressure-Overload Left Ventricular Hypertrophy In Vivo , 2013, The Journal of Nuclear Medicine.

[74]  M. Prentki,et al.  AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise. , 2003, Acta physiologica Scandinavica.

[75]  H. Langer,et al.  Platelets and the complement cascade in atherosclerosis , 2015, Front. Physiol..

[76]  E. Nisoli,et al.  Exercise training boosts eNOS-dependent mitochondrial biogenesis in mouse heart: role in adaptation of glucose metabolism. , 2014, American journal of physiology. Endocrinology and metabolism.

[77]  M. White,et al.  Insulin Receptor Substrates Are Essential for the Bioenergetic and Hypertrophic Response of the Heart to Exercise Training , 2014, Molecular and Cellular Biology.

[78]  B. Paigen,et al.  Genetic and genomic insights into the molecular basis of atherosclerosis. , 2007, Cell metabolism.

[79]  E. Clementi,et al.  Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome? , 2007, Circulation research.

[80]  P. Ponikowski,et al.  Experience from controlled trials of physical training in chronic heart failure. Protocol and patient factors in effectiveness in the improvement in exercise tolerance. European Heart Failure Training Group. , 1998, European heart journal.

[81]  Aruni Bhatnagar,et al.  Cardiovascular Effects and Benefits of Exercise , 2018, Front. Cardiovasc. Med..

[82]  M. Laughlin,et al.  Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain. , 2015, Progress in molecular biology and translational science.

[83]  D. Torella,et al.  Physiological cardiac remodelling in response to endurance exercise training: cellular and molecular mechanisms , 2011, Heart.

[84]  F. López‐Soriano,et al.  Effects of interleukin-15 (IL-15) on adipose tissue mass in rodent obesity models: evidence for direct IL-15 action on adipose tissue. , 2002, Biochimica et biophysica acta.

[85]  M. Silverman A view from the millennium: the practice of cardiology circa 1950 and thereafter. , 1999, Journal of the American College of Cardiology.

[86]  Simin Liu,et al.  Effects of Exercise Training on Cardiorespiratory Fitness and Biomarkers of Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials , 2015, Journal of the American Heart Association.

[87]  D. Thijssen,et al.  Impact of age, sex, and exercise on brachial artery flow-mediated dilatation. , 2009, American journal of physiology. Heart and circulatory physiology.

[88]  S. Keteyian,et al.  Cardiac rehabilitation exercise and self-care for chronic heart failure. , 2013, JACC. Heart failure.

[89]  V. Almendro,et al.  Interleukin-15 increases glucose uptake in skeletal muscle. An antidiabetogenic effect of the cytokine. , 2006, Biochimica et biophysica acta.

[90]  W. Kraus,et al.  Effects of exercise training amount and intensity on peak oxygen consumption in middle-age men and women at risk for cardiovascular disease. , 2005, Chest.

[91]  D. Gong,et al.  FSTL1 as a Potential Mediator of Exercise-Induced Cardioprotection in Post-Myocardial Infarction Rats , 2016, Scientific Reports.

[92]  Haiqin Tang,et al.  Cardiac rehabilitation in acute myocardial infarction patients after percutaneous coronary intervention , 2018, Medicine.

[93]  P. Wilson,et al.  Impact of body mass index on coronary heart disease risk factors in men and women. The Framingham Offspring Study. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[94]  Xinli Li,et al.  Exercise for the heart: signaling pathways , 2015, Oncotarget.

[95]  Y. Hellsten,et al.  Exercise‐Induced Capillary Growth in Human Skeletal Muscle and the Dynamics of VEGF , 2014, Microcirculation.

[96]  Gregory P. Samsa,et al.  Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: a randomised controlled trial , 2016, Diabetologia.

[97]  F. Epstein,et al.  Metabolic Changes in Spontaneously Hypertensive Rat Hearts Precede Cardiac Dysfunction and Left Ventricular Hypertrophy , 2019, Journal of the American Heart Association.

[98]  J. Eckel,et al.  Regulation of follistatin-like protein 1 expression and secretion in primary human skeletal muscle cells , 2013, Archives of physiology and biochemistry.

[99]  R. Bache,et al.  Regulation of coronary blood flow during exercise. , 2008, Physiological reviews.

[100]  C. R. Wilson,et al.  Adaptation and Maladaptation of the Heart in Obesity , 2008, Hypertension.

[101]  A. Lucia,et al.  Exercise is the real polypill. , 2013, Physiology.

[102]  D. Kitzman,et al.  Heart Failure: Exercise-Based Cardiac Rehabilitation: Who, When, and How Intense? , 2016, The Canadian journal of cardiology.

[103]  C. Weigert,et al.  Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations. , 2017, Cold Spring Harbor perspectives in medicine.

[104]  C. Celis-Morales,et al.  Exercise Modalities and Endothelial Function: A Systematic Review and Dose–Response Meta-Analysis of Randomized Controlled Trials , 2015, Sports Medicine.

[105]  Neil M. Johannsen,et al.  Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. , 2010, JAMA.

[106]  Shao-Cong Sun,et al.  NF-κB signaling in inflammation , 2017, Signal Transduction and Targeted Therapy.

[107]  M. Febbraio,et al.  Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase , 2009, Diabetologia.

[108]  M. Gassmann,et al.  Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells , 2011, Nature Medicine.

[109]  L. Opie,et al.  Metabolic mechanisms in heart failure. , 2007, Circulation.

[110]  F. Recchia,et al.  Follistatin‐like 1 promotes cardiac fibroblast activation and protects the heart from rupture , 2016, EMBO molecular medicine.

[111]  Torsten Doenst,et al.  Cardiac Metabolism in Heart Failure: Implications Beyond ATP Production , 2013, Circulation research.

[112]  A. Khera,et al.  Forecasting the Future of Cardiovascular Disease in the United States: A Policy Statement From the American Heart Association , 2011, Circulation.

[113]  Wei Zhang,et al.  The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis , 2009, BMC public health.

[114]  Stephen C. Kolwicz An "Exercise" in Cardiac Metabolism. , 2018, Frontiers in cardiovascular medicine.

[115]  L. Fontana Interventions to promote cardiometabolic health and slow cardiovascular ageing , 2018, Nature Reviews Cardiology.

[116]  N. Houstis,et al.  Using exercise to measure and modify cardiac function. , 2015, Cell metabolism.

[117]  S. Fritz,et al.  The association between resistance exercise and cardiovascular disease risk in women. , 2015, Journal of science and medicine in sport.

[118]  J. Sowers,et al.  The pathophysiology of hypertension in patients with obesity , 2014, Nature Reviews Endocrinology.

[119]  G. Heusch,et al.  TNFalpha in atherosclerosis, myocardial ischemia/reperfusion and heart failure. , 2010, Pharmacology & therapeutics.

[120]  J. Zierath,et al.  Exercise metabolism and the molecular regulation of skeletal muscle adaptation. , 2013, Cell metabolism.

[121]  Ralph A. DeFronzo,et al.  Reduced Skeletal Muscle Inhibitor of κBβ Content Is Associated With Insulin Resistance in Subjects With Type 2 Diabetes: Reversal by Exercise Training , 2006 .

[122]  P. Libby,et al.  Obesity, inflammation, and atherosclerosis , 2009, Nature Reviews Cardiology.

[123]  C. Handschin,et al.  Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise. , 2015, Bone.

[124]  W. Kraus,et al.  Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. , 2009, JAMA.

[125]  J. Sowers,et al.  The Renin Angiotensin Aldosterone System in Obesity and Hypertension: Roles in the Cardiorenal Metabolic Syndrome. , 2017, The Medical clinics of North America.

[126]  R. Touyz,et al.  Adipocytes Produce Aldosterone Through Calcineurin-Dependent Signaling Pathways: Implications in Diabetes Mellitus–Associated Obesity and Vascular Dysfunction , 2012, Hypertension.

[127]  Simon Briscoe,et al.  Exercise-based rehabilitation for heart failure. , 2014, The Cochrane database of systematic reviews.

[128]  S. Klein,et al.  Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized, controlled trial. , 2007, American journal of physiology. Endocrinology and metabolism.

[129]  B. Nicklas,et al.  Effect of exercise training on chronic inflammation. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[130]  H. Taegtmeyer,et al.  Adaptation and maladaptation of the heart in diabetes: Part I: general concepts. , 2002, Circulation.

[131]  Ò. Miró,et al.  Electron Transport Chain Defects in Heart Failure , 2002, Heart Failure Reviews.

[132]  P. Scherer,et al.  Adipose tissue, inflammation, and cardiovascular disease. , 2005, Circulation research.

[133]  S. Angadi,et al.  Exercise and Diet, Independent of Weight Loss, Improve Cardiometabolic Risk Profile in Overweight and Obese Individuals , 2011, The Physician and sportsmedicine.

[134]  D. Bernlohr,et al.  Insulin Stimulates Mitochondrial Fusion and Function in Cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 Signaling Pathway , 2013, Diabetes.

[135]  Véronique A. Cornelissen,et al.  Effects of Endurance Training on Blood Pressure, Blood Pressure–Regulating Mechanisms, and Cardiovascular Risk Factors , 2005, Hypertension.

[136]  P. Lin,et al.  Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study. , 2010, Archives of internal medicine.

[137]  H. Chung,et al.  Systemic adaptation to oxidative challenge induced by regular exercise. , 2008, Free radical biology & medicine.

[138]  M. LaMonte,et al.  Effects of Exercise Training on Chronic Inflammation in Obesity , 2013, Sports Medicine.

[139]  Youngil Lee,et al.  Mitochondrial Antioxidant Enzymes and Endurance Exercise-induced Cardioprotection against Ischemia-Reperfusion Injury , 2018 .

[140]  A. Støylen,et al.  High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction , 2017, Circulation.

[141]  P. Hojman,et al.  Muscle-to-organ cross talk mediated by myokines , 2012, Adipocyte.

[142]  C. Monaco,et al.  The Expression and Functions of Toll-Like Receptors in Atherosclerosis , 2010, Mediators of inflammation.

[143]  M. Piepoli,et al.  Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH) , 2004, BMJ : British Medical Journal.

[144]  L. Goodyear,et al.  Exercise regulation of adipose tissue , 2016, Adipocyte.

[145]  G. Lopaschuk,et al.  Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes. , 2016, Biochimica et biophysica acta.

[146]  Neil M. Johannsen,et al.  The role of exercise and physical activity in weight loss and maintenance. , 2014, Progress in cardiovascular diseases.

[147]  H. Daida,et al.  Neuron-Derived Neurotrophic Factor Ameliorates Adverse Cardiac Remodeling After Experimental Myocardial Infarction , 2015, Circulation. Heart failure.

[148]  J. B. Kim,et al.  Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. , 2006, Biochemical and biophysical research communications.

[149]  I. Zabetakis,et al.  Inflammation, not Cholesterol, Is a Cause of Chronic Disease , 2018, Nutrients.

[150]  T. Akinyemiju,et al.  Metabolic Syndrome Prevalence by Race/Ethnicity and Sex in the United States, National Health and Nutrition Examination Survey, 1988–2012 , 2017, Preventing chronic disease.

[151]  Marie-France Hivert,et al.  Sedentary Behavior and Cardiovascular Morbidity and Mortality: A Science Advisory From the American Heart Association , 2016, Circulation.

[152]  S. Tangye,et al.  Inflammatory Mechanisms in Obesity , 2013 .

[153]  J. Helge,et al.  Maintaining a clinical weight loss after intensive lifestyle intervention is the key to cardiometabolic health. , 2017, Obesity research & clinical practice.

[154]  Brian K. McFarlin,et al.  State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training , 2007 .

[155]  C. Folmes,et al.  Myocardial fatty acid metabolism in health and disease. , 2010, Physiological reviews.

[156]  Shah Ebrahim,et al.  Exercise-based rehabilitation for heart failure. , 2014, The Cochrane database of systematic reviews.

[157]  E. Abel,et al.  Insulin Signaling and Heart Failure. , 2016, Circulation research.

[158]  T. Murohara,et al.  Protective Roles of Adipocytokines and Myokines in Cardiovascular Disease. , 2016, Circulation journal : official journal of the Japanese Circulation Society.

[159]  M. Haykowsky,et al.  High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study. , 2015, Journal of applied physiology.

[160]  R. Ahima,et al.  Connecting Myokines and Metabolism , 2015, Endocrinology and metabolism.

[161]  M. Febbraio,et al.  Muscles, exercise and obesity: skeletal muscle as a secretory organ , 2012, Nature Reviews Endocrinology.

[162]  Simon Briscoe,et al.  Exercise-based rehabilitation for heart failure: systematic review and meta-analysis , 2015, Open Heart.

[163]  B. Pedersen,et al.  Exercise as a Mean to Control Low-Grade Systemic Inflammation , 2009, Mediators of inflammation.

[164]  D. Coyle,et al.  Effects of Aerobic Training, Resistance Training, or Both on Glycemic Control in Type 2 Diabetes , 2007, Annals of Internal Medicine.

[165]  M. Chew,et al.  Interleukin‐15 treatment improves glucose homeostasis and insulin sensitivity in obese mice , 2012, Diabetes, obesity & metabolism.

[166]  Roy Taylor,et al.  Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial , 2017, The Lancet.

[167]  A. Dendorfer,et al.  Angiotensin converting enzyme inhibition improves cardiac neuronal uptake of noradrenaline in spontaneously hypertensive rats , 2001, Journal of hypertension.

[168]  R. Bloomer,et al.  EFFECTS OF ACUTE AEROBIC AND ANAEROBIC EXERCISE ON BLOOD MARKERS OF OXIDATIVE STRESS , 2005, Journal of strength and conditioning research.

[169]  P. D. de Leeuw,et al.  The Link Between Adipose Tissue Renin-Angiotensin-Aldosterone System Signaling and Obesity-Associated Hypertension. , 2017, Physiology.

[170]  T. Murohara,et al.  Neuron-derived Neurotrophic Factor Functions as a Novel Modulator That Enhances Endothelial Cell Function and Revascularization Processes* , 2014, The Journal of Biological Chemistry.

[171]  Y. Hellsten,et al.  Differential regulation of IL-6 and TNF-α via calcineurin in human skeletal muscle cells , 2006 .

[172]  D. Harrison,et al.  Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training. , 2003, American journal of physiology. Heart and circulatory physiology.

[173]  K. Walsh,et al.  Follistatin-Like 1 Is an Akt-Regulated Cardioprotective Factor That Is Secreted by the Heart , 2008, Circulation.

[174]  A. Goldfine,et al.  Inflammation and insulin resistance. , 2006, The Journal of clinical investigation.

[175]  Stefan Neubauer,et al.  The failing heart--an engine out of fuel. , 2007, The New England journal of medicine.

[176]  Ralph B D'Agostino,et al.  Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. , 2002, Archives of internal medicine.

[177]  I. Laher,et al.  Exercise, Vascular Wall and Cardiovascular Diseases , 2008, Sports medicine.

[178]  Xiu-Li Kuang,et al.  Spatio-temporal expression of a novel neuron-derived neurotrophic factor (NDNF) in mouse brains during development , 2010, BMC Neuroscience.

[179]  Shah Ebrahim,et al.  Exercise training for systolic heart failure: Cochrane systematic review and meta‐analysis , 2010, European journal of heart failure.

[180]  M. Febbraio,et al.  The immunomodulating role of exercise in metabolic disease. , 2014, Trends in immunology.

[181]  A. Rocchini,et al.  Hypertension and Insulin Resistance Are Not Directly Related in Obese Dogs , 2004, Hypertension.

[182]  B. Saltin,et al.  Interleukin-6 stimulates lipolysis and fat oxidation in humans. , 2003, The Journal of clinical endocrinology and metabolism.

[183]  C. Baines,et al.  Cell biology of ischemia/reperfusion injury. , 2012, International review of cell and molecular biology.

[184]  A. Orekhov,et al.  Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis , 2016, BioMed research international.

[185]  R. Petrella,et al.  Effects of Exercise on Cardiovascular Risk Factors in Type 2 Diabetes , 2011, Diabetes Care.

[186]  J. Speakman,et al.  Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[187]  G. Sweeney,et al.  Cardiac remodeling in obesity. , 2008, Physiological reviews.

[188]  M. Laughlin,et al.  The coronary circulation in exercise training. , 2012, American journal of physiology. Heart and circulatory physiology.

[189]  G. Schuler,et al.  Regular Physical Activity Improves Endothelial Function in Patients With Coronary Artery Disease by Increasing Phosphorylation of Endothelial Nitric Oxide Synthase , 2003, Circulation.

[190]  Ian R. Lanza,et al.  Combined training enhances skeletal muscle mitochondrial oxidative capacity independent of age. , 2015, The Journal of clinical endocrinology and metabolism.

[191]  T. Murohara,et al.  Therapeutic Impact of Follistatin-Like 1 on Myocardial Ischemic Injury in Preclinical Models , 2012, Circulation.

[192]  A. Tedgui,et al.  [Atherosclerotic plaque formation]. , 1999, La Revue du praticien.

[193]  B. Pedersen,et al.  Beneficial health effects of exercise--the role of IL-6 as a myokine. , 2007, Trends in pharmacological sciences.

[194]  C. Vella,et al.  Cardiac function and arteriovenous oxygen difference during exercise in obese adults , 2011, European Journal of Applied Physiology.

[195]  W. Blaner,et al.  Lipids in the heart: a source of fuel and a source of toxins , 2007, Current opinion in lipidology.

[196]  M. Seldin,et al.  Myonectin (CTRP15), a Novel Myokine That Links Skeletal Muscle to Systemic Lipid Homeostasis* , 2012, The Journal of Biological Chemistry.

[197]  P. Calder,et al.  Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids , 2018, Nutrients.

[198]  P. Alvarez,et al.  Exercise And Heart Failure: Advancing Knowledge And Improving Care. , 2016, Methodist DeBakey cardiovascular journal.

[199]  J. Hawley,et al.  Update on the effects of physical activity on insulin sensitivity in humans , 2017, BMJ Open Sport & Exercise Medicine.

[200]  K. M. Popov,et al.  Regular exercise is associated with a protective metabolic phenotype in the rat heart. , 2004, American journal of physiology. Heart and circulatory physiology.

[201]  Fred S Apple,et al.  Third universal definition of myocardial infarction , 2012 .

[202]  Kristy L. Townsend,et al.  A Novel Role for Subcutaneous Adipose Tissue in Exercise-Induced Improvements in Glucose Homeostasis , 2015, Diabetes.

[203]  D. James,et al.  Interleukin-6 Increases Insulin-Stimulated Glucose Disposal in Humans and Glucose Uptake and Fatty Acid Oxidation In Vitro via AMP-Activated Protein Kinase , 2006, Diabetes.

[204]  R. Virmani,et al.  Mechanisms of Plaque Formation and Rupture , 2014 .

[205]  Hung‐wen Liu,et al.  Moderate Exercise Suppresses NF-κB Signaling and Activates the SIRT1-AMPK-PGC1α Axis to Attenuate Muscle Loss in Diabetic db/db Mice , 2018, Front. Physiol..

[206]  M. Blanchette,et al.  Genome-wide Orchestration of Cardiac Functions by the Orphan Nuclear Receptors ERRα and γ , 2007 .