Association of Cardiopulmonary Exercise Capacity and Adipokines in the General Population

Abstract

Adipokines and cardiorespiratory fitness (CRF) are associated with the (patho)physiology of cardiometabolic diseases. Whether CRF and adipokines are related is unclear. We investigated associations of CRF with leptin, adiponectin, chemerin, resistin and vaspin. Data from the population-based Study of Health in Pomerania was used (n=1,479; median age 49 years; 51% women). Cardiopulmonary exercise testing was used to measure CRF. Circulating adipokine concentrations were measured by enzyme-linked immunosorbent assay. The association between CRF and adipokines was assessed using multivariable sex-specific quantile regression models. Higher maximum oxygen uptake was significantly associated with lower leptin (men:−0.11 ng/ml; 95%-confidence interval [CI]:−0.18 to−0.03 ng/ml; p<0.005; women:−0.17 ng/ml; 95%-CI:−0.33 to−0.02 ng/ml; p<0.05) and chemerin (men:−0.26 ng/ml; 95%-CI:−0.52 to−0.01 ng/ml; p<0.05; women:−0.41 ng/ml; 95%-CI:−0.82 to−0.01 ng/ml; p<0.05) as well as higher adiponectin concentrations (men: 0.06 µg/ml; 95%-CI: 0.02 to 0.11 µg/ml; p<0.05; women: 0.03 µg/ml; 95%-CI:−0.05 to 0.10 µg/ml; p=0.48). We found that CRF was inversely associated with leptin and chemerin in both sexes and positively associated with adiponectin only in men.

Key words

adipokines - cardio-respiratory fitness - epidemiology

Publication History

Received: 29 April 2021

Accepted: 02 November 2021

Article published online:
03 February 2022

• References

• 1 WHO. Obesity and Overweight, 2020. In Internet: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweightaccessed 03.03.2020
• 2 Kodama S, Saito K, Tanaka S. et al. Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA 2009; 301: 2024-2035
• 3 Heron M, Anderson RN. Changes in the leading cause of death: recent patterns in heart disease and cancer mortality. NCHS Data Brief 2016; 1-8
• 4 Miele EM, Headley SAE. The effects of chronic aerobic exercise on cardiovascular risk factors in persons with diabetes mellitus. Curr Diab Rep 2017; 17: 97
• 5 Freitas Lima LC, Braga VdA, do Socorro de França Silva M. et al. Adipokines, diabetes and atherosclerosis: an inflammatory association. Front Physiol 2015; 6: 304
• 6 Lehr S, Hartwig S, Sell H. Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl 2012; 6: 91-101
• 7 Blüher M. Adipokines – removing road blocks to obesity and diabetes therapy. Mol Metab 2014; 3: 230-240
• 8 Graßmann S, Wirsching J, Eichelmann F. et al. Association between peripheral adipokines and inflammation markers: A systematic review and meta-analysis. Obesity (Silver Spring) 2017; 25: 1776-1785
• 9 Bjornstad P, Cree-Green M, Baumgartner A. et al. Leptin is associated with cardiopulmonary fitness independent of body-mass index and insulin sensitivity in adolescents with type 1 diabetes: a brief report from the EMERALD study. J Diabetes Complications 2017; 31: 850-853
• 10 Miyatake N, Murakami H, Kawakami R. et al. Circulating leptin levels are associated with physical activity or physical fitness in Japanese. Environ Health Prev Med 2014; 19: 362-366
• 11 Martinez EC, Fortes MdSR, Anjos LA. Influence of nutritional status and VO2max on adiponectin levels in men older than 35 years. corrected. Arq Bras Cardiol 2011; 96: 471-476
• 12 Agostinis-Sobrinho C, Moreira C, Abreu S. et al. Serum adiponectin levels and cardiorespiratory fitness in nonoverweight and overweight portuguese adolescents: The labmed physical activity study. Pediatr Exerc Sci 2017; 29: 237-244
• 13 Chang E, Varghese M, Singer K. Gender and sex differences in adipose tissue. Curr Diab Rep 2018; 18: 69
• 14 White UA, Tchoukalova YD. Sex dimorphism and depot differences in adipose tissue function. Biochim Biophys Acta 2014; 1842: 377-392
• 15 Valencak TG, Osterrieder A, Schulz TJ. Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism. Redox Biol 2017; 12: 806-813
• 16 Nawrocki AR, Scherer PE. Keynote review: The adipocyte as a drug discovery target. Drug Discov Today 2005; 10: 1219-1230
• 17 Chruściel P, Sahebkar A, Rembek-Wieliczko M. et al. Impact of statin therapy on plasma adiponectin concentrations: A systematic review and meta-analysis of 43 randomized controlled trial arms. Atherosclerosis 2016; 253: 194-208
• 18 Abbas NAT, El Salem A. Metformin, sitagliptin, and liraglutide modulate serum retinol-binding protein-4 level and adipocytokine production in type 2 diabetes mellitus rat model. Can J Physiol Pharmacol 2018; 96: 1226-1231
• 19 Völzke H, Alte D, Schmidt CO. et al. Cohort profile: the study of health in Pomerania. Int J Epidemiol 2011; 40: 294-307
• 20 Harriss DJ, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817
• 21 Winter T, Friedrich N, Lamp S et al. The integrated research biobank of the university medicine greifswald. Open Journal of Bioresources 2020; 7; 2
• 22 Jones NL, Makrides L, Hitchcock C. et al. Normal standards for an incremental progressive cycle ergometer test. Am Rev Respir Dis 1985; 131: 700-708
• 23 Wasserman K. Principles of exercise testing and interpretation: Including pathophysiology and clinical applications. 5th ed Philadelphia, Pa: Kluwer/Lippincott Williams & Wilkins; 2012
• 24 Rabe K, Lehrke M, Parhofer KG. et al. Adipokines and insulin resistance. Mol Med 2008; 14: 741-751
• 25 Lee S, Norheim F, Langleite TM. et al. Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight. Diabetologia 2019; 62: 1048-1064
• 26 You T, Nicklas BJ. Effects of exercise on adipokines and the metabolic syndrome. Curr Diab Rep 2008; 8: 7-11
• 27 Malin SK, Niemi N, Solomon TPJ. et al. Exercise training with weight loss and either a high- or low-glycemic index diet reduces metabolic syndrome severity in older adults. Ann Nutr Metab 2012; 61: 135-141
• 28 Haus JM, Solomon TPJ, Marchetti CM. et al. Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance. J Clin Endocrinol Metab 2010; 95: 323-327
• 29 Kelly KR, Haus JM, Solomon TPJ. et al. A low-glycemic index diet and exercise intervention reduces TNF(alpha) in isolated mononuclear cells of older, obese adults. J Nutr 2011; 141: 1089-1094
• 30 Blüher M. Metabolically healthy obesity. Endocr Rev. 2020 41: bnaa004.
• 31 DeFina LF, Haskell WL, Willis BL. et al. Physical activity versus cardiorespiratory fitness: two (partly) distinct components of cardiovascular health?. Prog Cardiovasc Dis 2015; 57: 324-329
• 32 Bouchard C, An P, Rice T. et al. Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study. J Appl Physiol (1985) 1999; 87: 1003-1008
• 33 Booth FW, Roberts CK, Thyfault JP. et al. Role of inactivity in chronic diseases: Evolutionary insight and pathophysiological mechanisms. Physiol Rev 2017; 97: 1351-1402
• 34 Fedewa MV, Hathaway ED, Ward-Ritacco CL. et al. The effect of chronic exercise training on leptin: A systematic review and meta-analysis of randomized controlled trials. Sports Med 2018; 48: 1437-1450
• 35 Bjornstad P, Cree-Green M, Baumgartner A. et al. Leptin is associated with cardiopulmonary fitness independent of body-mass index and insulin sensitivity in adolescents with type 1 diabetes: a brief report from the EMERALD study. J Diabetes Complications 2017; 31: 850-853
• 36 Cicchella A, Stefanelli C, Purge P. et al. The associations between peak O2 consumption and leptin in 10- to 12-year-old boys. Clin Physiol Func Imaging 2013; 33: 313-316
• 37 Gar C, Rottenkolber M, Grallert H. et al. Physical fitness and plasma leptin in women with recent gestational diabetes. PLoS One 2017; 12: e0179128
• 38 Malin SK, Navaneethan SD, Mulya A. et al. Exercise-induced lowering of chemerin is associated with reduced cardiometabolic risk and glucose-stimulated insulin secretion in older adults. J Nutr Health Aging 2014; 18: 608-615
• 39 Sell H, Divoux A, Poitou C. et al. Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. J Clin Endicronol Metab 2010; 95: 2892-2896
• 40 Chakaroun R, Raschpichler M, Klöting N. et al. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism 2012; 61: 706-714
• 41 Shin H-Y, Park S, Lee JW. Positive association between the changes in chemerin and adiponectin levels after weight reduction. Endocr Res 2017; 42: 287-295
• 42 Venojärvi M, Wasenius N, Manderoos S. et al. Nordic walking decreased circulating chemerin and leptin concentrations in middle-aged men with impaired glucose regulation. Ann Med 2013; 45: 162-170
• 43 Saremi A, Shavandi N, Parastesh M. et al. Twelve-week aerobic training decreases chemerin level and improves cardiometabolic risk factors in overweight and obese men. Asian J Sports Med 2010; 1: 151-158
• 44 Kolahdouzi S, Baghadam M, Kani-Golzar FA. et al. Progressive circuit resistance training improves inflammatory biomarkers and insulin resistance in obese men. Pysiol Behav 2019; 205: 15-21
• 45 Ouerghi N, Fradj MKB, Khammassi M. et al. Plasma chemerin in young untrained men: association with cardio-metabolic traits and physical performance, and response to intensive interval training. Neuro Endocrinol Lett 2017; 38: 59-66
• 46 Ye R, Scherer PE. Adiponectin, driver or passenger on the road to insulin sensitivity?. Mol Metab 2013; 2: 133-141
• 47 Iwabu M, Okada-Iwabu M, Yamauchi T. et al. Adiponectin/adipor research and its implications for lifestyle-related diseases. Front Cardiovasc Med 2019; 6: 116
• 48 Park KM, Park SC, Kang S. Effects of resistance exercise on adipokine factors and body composition in pre- and postmenopausal women. J Exerc Rehabil 2019; 15: 676-682
• 49 Martinez-Huenchullan SF, Tam CS, Ban LA. et al. Skeletal muscle adiponectin induction in obesity and exercise. Metabolism 2020; 102: 154008
• 50 Krause MP, Milne KJ, Hawke TJ. Adiponectin-consideration for its role in skeletal muscle health. Int J Mol Sci 2019; 20
• 51 Martinez-Huenchullan SF, Maharjan BR, Williams PF. et al. Differential metabolic effects of constant moderate versus high intensity interval training in high-fat fed mice: possible role of muscle adiponectin. Physiol Rep 2018; 6
• 52 Rubin DA, McMurray RG, Harrell JS. et al. The association between insulin resistance and cytokines in adolescents: the role of weight status and exercise. Metabolism 2008; 57: 683-690
• 53 McVean JJF, Carrel AL, Eickhoff JC. et al. Fitness level and body composition are associated with inflammation in non-obese children. J Pediatr Endocrinol Metab 2009; 22: 153-159
• 54 Steppan CM, Bailey ST, Bhat S. et al. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307-312
• 55 Acquarone E, Monacelli F, Borghi R. et al. Resistin: A reappraisal. Mech Ageing Dev 2019; 178: 46-63
• 56 Escoté X, Gómez-Zorita S, López-Yoldi M. et al. Role of Omentin, Vaspin, Cardiotrophin-1, TWEAK and NOV/CCN3 in obesity and diabetes development. Int J Mol Sci 2017; 18: 1770
• 57 Dimova R, Tankova T. The role of vaspin in the development of metabolic and glucose tolerance disorders and atherosclerosis. Biomed Res Int 2015; 2015: 823481
• 58 Li K, Li L, Yang M. et al. Short-term continuous subcutaneous insulin infusion decreases the plasma vaspin levels in patients with type 2 diabetes mellitus concomitant with improvement in insulin sensitivity. Eur J Endocrinol 2011; 164: 905-910
• 59 Faramarzi M, Banitalebi E, Nori S. et al. Effects of rhythmic aerobic exercise plus core stability training on serum omentin, chemerin and vaspin levels and insulin resistance of overweight women. J Sports Med Phys Fitness 2016; 56: 476-482
• 60 Jia GY, Han T, Gao L. et al. Effect of aerobic exercise and resistance exercise in improving non-alcoholic fatty liver disease: a randomized controlled trial. Zhonghua Gan Zang Bing Za Zhi 2018; 26: 34-41
• 61 Amouzad Mahdirejei H, Fadaei Reyhan Abadei S, Abbaspour Seidi A. et al. Effects of an eight-week resistance training on plasma vaspin concentrations, metabolic parameters levels and physical fitness in patients with type 2 diabetes. Cell J 2014; 16: 367-374
• 62 Sahebkar A, Giua R, Pedone C. Impact of statin therapy on plasma leptin concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Br J Clin Pharmacol 2016; 82: 1674-1684
• 63 Bahls M, Groß S, Ittermann T. et al. Statins are related to impaired exercise capacity in males but not females. PLoS One 2017; 12: e0179534
• 64 Hamasaki H. Effects of glucose-lowering agents on cardiorespiratory fitness. World J Diabetes 2018; 9: 230-238
• 65 Luo L, Liu M. Adipose tissue in control of metabolism. J Endocrinol 2016; 231: R77-R99