Adiponectin as novel biomarker of endothelial dysfunction in insulin resistance and obesity – a narrative review
DOI:
https://doi.org/10.12775/JEHS.2020.10.09.071Keywords
adiponectin, insulin resistance, obesity, vascular dysfunctionAbstract
Introduction: Obesity is a chronic fatal disease with still growing incidence among children, adolescents, and adults worldwide. The subclinical inflammatory process together with hipoadiponectinemia may lead to the development of various comorbidities, including cardiovascular complications. That is why, the relationship between adipose tissue activity, obesity, insulin resistance, and endothelial function is in high interest and an object of extensively studies.
Aim of the study: This article summarizes the current knowledge on the anti-atherogenic effects of adiponectin and its properties to improve endothelial function in obesity-related insulin resistance.
Description of knowledge: Adiponectin, an adipose tissue-derived pleiotropic hormone with anti-inflammatory, anti-atherogenic, anti-diabetic, and insulin-sensitizing actions, is not only engaged in modulation of type 2 diabetes mellitus, hypertension or coronary artery disease, but the latest researches highlight its role in improving vascular wall integrity. It affects complex signaling pathways in endothelial cells and influence inflammatory responses in the subendothelial space. Pre-clinical and clinical studies suggest that agents leading to increase in adiponectin levels, simultaneously contribute to decrease insulin resistance, and improve endothelial dysfunction.
Conclusions: Adiponectin may be a predictive factor of endothelial dysfunctionality and vascular remodeling development in the group of patients with overweight, obesity, and insulin resistance. Discovering pharmacological agents and non-pharmacological interventions that increase the level of circulating adiponectin will become novel and innovative therapeutic strategy to ameliorate obesity-related comorbidities. Therefore, further studies are required to determine the exact role of adiponectin in the pathogenesis of metabolic diseases.
References
Engin A. The Definition and Prevalence of Obesity and Metabolic Syndrome. Adv Exp Med Biol. 2017;960:1-17. doi:10.1007/978-3-319-48382-5_1.
Owens TM. Morbid obesity: the disease and comorbidities. Crit Care Nurs Q. 2003;26(2):162-165. doi:10.1097/00002727-200304000-00011.
Elagizi A, Kachur S, Lavie CJ, Carbone S, Pandey A, Ortega FB, et al. An Overview and Update on Obesity and the Obesity Paradox in Cardiovascular Diseases. Prog Cardiovasc Dis. 2018;61(2):142-150. doi:10.1016/j.pcad.2018.07.003.
Kramer H, Cao G, Dugas L, Luke A, Cooper R, Durazo-Arvizu R. Increasing BMI and waist circumference and prevalence of obesity among adults with Type 2 diabetes: the National Health and Nutrition Examination Surveys. J Diabetes Complications. 2010;24(6):368-374. doi:10.1016/j.jdiacomp.2009.10.001.
Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond). 2008;32(9):1431-1437. doi:10.1038/ijo.2008.102.
Andolfi C, Fisichella PM. Epidemiology of Obesity and Associated Comorbidities. J Laparoendosc Adv Surg Tech A. 2018;28(8):919-924. doi:10.1089/lap.2018.0380.
Prospective Studies Collaboration, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083-1096. doi:10.1016/S0140-6736(09)60318-4.
Murphy N, Cross AJ, Abubakar M, Jenab M, Aleksandrova K, Boutron-Ruault MC, et al. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). PLoS Med. 2016;13(4):e1001988. doi:10.1371/journal.pmed.1001988.
Boeing H, Weisgerber UM, Jeckel A, Rose HJ, Kroke A. Association between glycated hemoglobin and diet and other lifestyle factors in a nondiabetic population: cross-sectional evaluation of data from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition Study. Am J Clin Nutr. 2000;71(5):1115-1122. doi:10.1093/ajcn/71.5.1115.
Lear SA, James PT, Ko GT, Kumanyika S. Appropriateness of waist circumference and waist-to-hip ratio cutoffs for different ethnic groups. Eur J Clin Nutr. 2010;64(1):42-61. doi:10.1038/ejcn.2009.70.
Poulos SP, Hausman DB, Hausman GJ. The development and endocrine functions of adipose tissue. Mol Cell Endocrinol. 2010;323(1):20-34. doi:10.1016/j.mce.2009.12.011.
Smekal A, Vaclavik J. Adipokines and cardiovascular disease: A comprehensive review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017;161(1):31-40. doi:10.5507/bp.2017.002.
Unamuno X, Gómez-Ambrosi J, Rodríguez A, Becerril S, Frühbeck G, Catalán V. Adipokine dysregulation and adipose tissue inflammation in human obesity. Eur J Clin Invest. 2018;48(9):e12997. doi:10.1111/eci.12997.
Landecho MF, Tuero C, Valentí V, Bilbao I, de la Higuera M, Frühbeck G. Relevance of Leptin and Other Adipokines in Obesity-Associated Cardiovascular Risk. Nutrients. 2019;11(11):2664. doi:10.3390/nu11112664.
Shehzad A, Iqbal W, Shehzad O, Lee YS. Adiponectin: regulation of its production and its role in human diseases. Hormones (Athens). 2012;11(1):8-20. doi:10.1007/BF03401534.
Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, Revett T, Gimeno R, Lodish HF. Molecular, biochemical and functional characterizations of C1q/TNF family members: adipose-tissue-selective expression patterns, regulation by PPAR-gamma agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions. Biochem J. 2008;416(2):161-177. doi:10.1042/BJ20081240.
Ortiz Segura MDC, Del Río Navarro BE, Rodríguez Espino BA, Marchat LA, Sánchez Muñoz F, Villafaña S, et al. Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance. Endocr Res. 2017;42(3):252-259. doi:10.1080/07435800.2017.1294601.
Liberale L, Bonaventura A, Vecchiè A, Casula M, Dallegri F, Montecucco F, et al. The Role of Adipocytokines in Coronary Atherosclerosis [published correction appears in Curr Atheroscler Rep. 2017 May;19(5):21]. Curr Atheroscler Rep. 2017;19(2):10. doi:10.1007/s11883-017-0644-3.
Nakamura K, Fuster JJ, Walsh K. Adipokines: a link between obesity and cardiovascular disease. J Cardiol. 2014;63(4):250-259. doi:10.1016/j.jjcc.2013.11.006.
Adeva-Andany MM, Martínez-Rodríguez J, González-Lucán M, Fernández-Fernández C, Castro-Quintela E. Insulin resistance is a cardiovascular risk factor in humans. Diabetes Metab Syndr. 2019;13(2):1449-1455. doi:10.1016/j.dsx.2019.02.023.
Rohde K, Keller M, la Cour Poulsen L, Blüher M, Kovacs P, Böttcher Y. Genetics and epigenetics in obesity. Metabolism. 2019;92:37-50. doi:10.1016/j.metabol.2018.10.007.
Saltiel AR, Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest. 2017;127(1):1-4. doi:10.1172/JCI92035.
Murano I, Barbatelli G, Parisani V, Latini C, Muzzonigro G, Castellucci M, et al. Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res. 2008;49(7):1562-1568. doi:10.1194/jlr.M800019-JLR200.
Sun K, Tordjman J, Clément K, Scherer PE. Fibrosis and adipose tissue dysfunction. Cell Metab. 2013;18(4):470-477. doi:10.1016/j.cmet.2013.06.016.
Crewe C, An YA, Scherer PE. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. J Clin Invest. 2017;127(1):74-82. doi:10.1172/JCI88883.
Rodríguez A, Ezquerro S, Méndez-Giménez L, Becerril S, Frühbeck G. Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism. Am J Physiol Endocrinol Metab. 2015;309(8):E691-E714. doi:10.1152/ajpendo.00297.2015.
Kwaifa IK, Bahari H, Yong YK, Noor SM. Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications. Biomolecules. 2020;10(2):291. doi:10.3390/biom10020291.
Balsan GA, Vieira JL, Oliveira AM, Portal VL. Relationship between adiponectin, obesity and insulin resistance. Rev Assoc Med Bras (1992). 2015;61(1):72-80. doi:10.1590/1806-9282.61.01.072.
Smitka K, Marešová D. Adipose Tissue as an Endocrine Organ: An Update on Pro-inflammatory and Anti-inflammatory Microenvironment. Prague Med Rep. 2015;116(2):87-111. doi:10.14712/23362936.2015.49.
Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita M. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem. 1996;120(4):803-812. doi:10.1093/oxfordjournals.jbchem.a021483.
Metin Aksu N, Yazgan Aksoy D, Akkaş M, Çinar N, Uçar F, Bülent Yildiz O, et al. Adiponectin levels decrease independently of body mass index and diabetes type after the normalization of hyperglycemia. Turk J Med Sci. 2020;50(2):312-315. doi:10.3906/sag-1903-35.
Engin A. Adiponectin-Resistance in Obesity. Adv Exp Med Biol. 2017;960:415-441. doi:10.1007/978-3-319-48382-5_18.
Kocełak P, Chudek J, Olszanecka-Glinianowicz M. Prevalence of metabolic syndrome and insulin resistance in overweight and obese women according to the different diagnostic criteria. Minerva Endocrinol. 2012;37(3):247-254.
Caceres M, Teran CG, Rodriguez S, Medina M. Prevalence of insulin resistance and its association with metabolic syndrome criteria among Bolivian children and adolescents with obesity. BMC Pediatr. 2008;8:31. doi:10.1186/1471-2431-8-31.
Bacha F, Saad R, Gungor N, Arslanian SA. Adiponectin in youth: relationship to visceral adiposity, insulin sensitivity, and beta-cell function. Diabetes Care. 2004;27(2):547-552. doi:10.2337/diacare.27.2.547.
Ayina CN, Noubiap JJ, Etoundi Ngoa LS, Boudou F, Gautier JF, Mengnjo MK, et al. Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population. Lipids Health Dis. 2016;15:96. doi:10.1186/s12944-016-0264-x.
Han SJ, Boyko EJ, Fujimoto WY, Kahn SE, Leonetti DL. Low Plasma Adiponectin Concentrations Predict Increases in Visceral Adiposity and Insulin Resistance. J Clin Endocrinol Metab. 2017;102(12):4626-4633. doi:10.1210/jc.2017-01703.
Hara K, Horikoshi M, Yamauchi T, et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care. 2006;29(6):1357-1362. doi:10.2337/dc05-1801.
Liu W, Zhou X, Li Y, Zhang S, Cai X, Zhang R, et al. Serum leptin, resistin, and adiponectin levels in obese and non-obese patients with newly diagnosed type 2 diabetes mellitus: A population-based study. Medicine (Baltimore). 2020;99(6):e19052. doi:10.1097/MD.0000000000019052.
Kuo SM, Halpern MM. Lack of association between body mass index and plasma adiponectin levels in healthy adults. Int J Obes (Lond). 2011;35(12):1487-1494. doi:10.1038/ijo.2011.20.
Mongraw-Chaffin M, Foster MC, Anderson CAM, Kalyani RR, Vaidya D, Burke GL, et al. Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk. J Am Coll Cardiol. 2018;71(17):1857-1865. doi:10.1016/j.jacc.2018.02.055.
Smith GI, Mittendorfer B, Klein S. Metabolically healthy obesity: facts and fantasies. J Clin Invest. 2019;129(10):3978-3989. doi:10.1172/JCI129186.
Stefan N, Häring HU, Schulze MB. Metabolically healthy obesity: the low-hanging fruit in obesity treatment?. Lancet Diabetes Endocrinol. 2018;6(3):249-258. doi:10.1016/S2213-8587(17)30292-9.
Eckel N, Meidtner K, Kalle-Uhlmann T, Stefan N, Schulze MB. Metabolically healthy obesity and cardiovascular events: A systematic review and meta-analysis. Eur J Prev Cardiol. 2016;23(9):956-966. doi:10.1177/2047487315623884.
Engin A. Endothelial Dysfunction in Obesity. Adv Exp Med Biol. 2017;960:345-379. doi:10.1007/978-3-319-48382-5_15.
Muñoz-Muñoz E, Krause BJ, Uauy R, Casanello P. LGA-newborn from patients with pregestational obesity present reduced adiponectin-mediated vascular relaxation and endothelial dysfunction in fetoplacental arteries. J Cell Physiol. 2018;233(10):6723-6733. doi:10.1002/jcp.26499.
Satish M, Saxena SK, Agrawal DK. Adipokine Dysregulation and Insulin Resistance with Atherosclerotic Vascular Disease: Metabolic Syndrome or Independent Sequelae?. J Cardiovasc Transl Res. 2019;12(5):415-424. doi:10.1007/s12265-019-09879-0.
Oishi JC, Castro CA, Silva KA, Fabricio V, Cárnio EC, Phillips SA, et al. Endothelial Dysfunction and Inflammation Precedes Elevations in Blood Pressure Induced by a High-Fat Diet [published correction appears in Arq Bras Cardiol. 2019 Jan;112(1):116]. Arq Bras Cardiol. 2018;110(6):558-567. doi:10.5935/abc.20180086.
Ohashi K, Kihara S, Ouchi N, Kumada M, Fujita K, Hiuge A, et al. Adiponectin replenishment ameliorates obesity-related hypertension [published correction appears in Hypertension. 2007;49(2):e14]. Hypertension. 2006;47(6):1108-1116. doi:10.1161/01.HYP.0000222368.43759.a1.
Li R, Wang WQ, Zhang H, Yang X, Fan Q, Christopher TA, et al. Adiponectin improves endothelial function in hyperlipidemic rats by reducing oxidative/nitrative stress and differential regulation of eNOS/iNOS activity. Am J Physiol Endocrinol Metab. 2007;293(6):E1703-E1708. doi:10.1152/ajpendo.00462.2007.
Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda M, et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem. 2002;277(40):37487-37491. doi:10.1074/jbc.M206083200.
Beatty AL, Zhang MH, Ku IA, Na B, Schiller NB, Whooley MA. Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: data from the Heart and Soul Study. Atherosclerosis. 2012;220(2):587-592. doi:10.1016/j.atherosclerosis.2011.11.038.
Achari AE, Jain SK. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int J Mol Sci. 2017;18(6):1321. doi:10.3390/ijms18061321.
Han SH, Quon MJ, Kim JA, Koh KK. Adiponectin and cardiovascular disease: response to therapeutic interventions. J Am Coll Cardiol. 2007;49(5):531-538. doi:10.1016/j.jacc.2006.08.061.
Korybalska K, Luczak J, Swora-Cwynar E, Kanikowska A, Czepulis N, Kanikowska D, et al. Weight loss-dependent and -independent effects of moderate calorie restriction on endothelial cell markers in obesity. J Physiol Pharmacol. 2017;68(4):597-608.
Rocha-Rodrigues S, Gonçalves IO, Beleza J, Ascensão A, Magalhães J. Physical exercise mitigates high-fat diet-induced adiposopathy and related endocrine alterations in an animal model of obesity. J Physiol Biochem. 2018;74(2):235-246. doi:10.1007/s13105-018-0609-1.
Corbi G, Polito R, Monaco ML, Cacciatore F, Scioli M, Ferrara N, et al. Adiponectin Expression and Genotypes in Italian People with Severe Obesity Undergone a Hypocaloric Diet and Physical Exercise Program. Nutrients. 2019;11(9):2195. doi:10.3390/nu11092195.
Calvani M, Scarfone A, Granato L, Mora EV, Nanni G, Castagneto M, et al. Restoration of adiponectin pulsatility in severely obese subjects after weight loss. Diabetes. 2004;53(4):939-947. doi:10.2337/diabetes.53.4.939.
Huang F, Del-Río-Navarro BE, Leija-Martinez J, Torres-Alcantara S, Ruiz-Bedolla E, Hernández-Cadena L, et al. Effect of omega-3 fatty acids supplementation combined with lifestyle intervention on adipokines and biomarkers of endothelial dysfunction in obese adolescents with hypertriglyceridemia. J Nutr Biochem. 2019;64:162-169. doi:10.1016/j.jnutbio.2018.10.012.
Chai F, Wang Y, Zhou Y, Liu Y, Geng D, Liu J. Adiponectin downregulates hyperglycemia and reduces pancreatic islet apoptosis after roux-en-y gastric bypass surgery. Obes Surg. 2011;21(6):768-773. doi:10.1007/s11695-011-0357-6.
Wolf RM, Jaffe AE, Steele KE, Schweitzer MA, Magnuson TH, Wolfe A, et al. Cytokine, Chemokine, and Cytokine Receptor Changes Are Associated With Metabolic Improvements After Bariatric Surgery. J Clin Endocrinol Metab. 2019;104(3):947-956. doi:10.1210/jc.2018-02245.
Farias G, Netto BDM, Boritza K, Bettini SC, Vilela RM, Dâmaso AR. Impact of Weight Loss on Inflammation State and Endothelial Markers Among Individuals with Extreme Obesity After Gastric Bypass Surgery: a 2-Year Follow-up Study. Obes Surg. 2020;30(5):1881-1890. doi:10.1007/s11695-020-04411-9.
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