Associations of adipokines and metabolic hormones with low-density lipoprotein hypercholesterolemia in men and women under 45 years of age
https://doi.org/10.18087/cardio.2022.11.n2239
Abstract
Aim To study the adipokine profile in young people with hypercholesterolemia and low-density lipoproteins (LDL) and to evaluate the relationship between concentrations of LDL cholesterol (LDL-C) and metabolic hormones in men and women younger than 45 years.
Material and methods This study included 304 subjects (group 1, 56 men with LDL-C concentration <2.1 mmol/l; group 2, 87 men with LDL-C concentration ≥4.2 mmol/l; group 3, 90 women with LDL-C concentration <2.1 mmol/l; and group 4, 71 women with LDL-C concentration ≥4.2 mmol/l). Serum concentrations of total cholesterol (C), triglycerides (TG), high-density lipoprotein C, and glucose were measured by an enzymatic assay with ThermoFisher Scientific kits and a KonelabPrime 30i biochemical analyzer. LDL-C was calculated using the Friedewald’s formula. Concentrations of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, interleukin 6, insulin, leptin, monocyte chemotactic protein 1 (MCP-1), pancreatic polypeptide (PP), peptide YY (PYY), tumor necrosis factor alpha (TNF-α), adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor 1 (PAI-1), and resistin were measured by multiplex analysis (Human Metabolic Hormone V3 and Human Adipokine Panel 1 panels).
Results The groups differed in traditional cardiometabolic risk factors. In the male and female patient groups with LDL-C ≥4.2 mmol/l, the prevalence of impaired fasting glucose, incidence of insulin resistance, TG, and TC were higher than in subjects with LDL-C <2.1 mmol/l. The odds for the presence of LDL hypercholesterolemia (LDL-C ≥4.2 mmol/l) were significantly associated with increased concentrations of C-peptide and lipocalin-2 in men and with increased concentrations of lipocalin-2 and decreased concentrations of GLP-1 in women (р<0.05).
Conclusion Increased concentrations of LDL-C in young people were associated with changes in the adipokine profile and with the presence of metabolic syndrome components. These results were confirmed by changes in blood concentrations of metabolic markers that characterize disorders of metabolic processes.
Keywords
About the Authors
Е. V. KashtanovaRussian Federation
Leading researcher Laboratory of Clinical Biochemical and Hormonal Studies on Internal Diseases
Novosibirsk, Russia
Yа. V. Polonskaya
Russian Federation
Senior Researcher at the Laboratory of Clinical Biochemical and Hormonal Studies of Internal Diseases
Novosibirsk, Russia
V. S. Shramko
Russian Federation
Researcher at the Laboratory of Clinical Biochemical and Hormonal Studies of Internal Diseases
Novosibirsk, Russia
L. V. Shcherbakova
Russian Federation
Senior Researcher at the Laboratory of Clinical-Populational and Prophylactic Studies on Internal and Endocrine Diseases
Novosibirsk, Russia
Е. М. Stakhneva
Russian Federation
Senior Researcher at the Laboratory of Clinical Biochemical and Hormonal Studies of Internal Diseases
Novosibirsk, Russia
E. V. Sadovski
Russian Federation
Researcher at the Laboratory of Clinical Biochemical and Hormonal Studies of Internal Diseases
Novosibirsk, Russia
A. N. Spiridonov
Russian Federation
postgraduate IIPM – Branch of IC&G SB RAS
Novosibirsk, Russia
Yu. I. Ragino
Russian Federation
Head of IIPM – Branch of IC&G SB RAS
Novosibirsk, Russia
References
1. Kallio P, Pahkala K, Heinonen OJ, Tammelin TH, Palve K, Hirvensalo M et al. Physical inactivity from youth to adulthood and adult cardiometabolic risk profile. Preventive Medicine. 2021;145:106433. DOI: 10.1016/j.ypmed.2021.106433
2. Kim JS, Chen Z, Alderete TL, Toledo-Corral C, Lurmann F, Berhane K et al. Associations of air pollution, obesity and cardiometabolic health in young adults: The Meta-AIR study. Environment International. 2019;133(Pt A):105180. DOI: 10.1016/j.envint.2019.105180
3. Zvolinskaya E.Yu., Kimitsidi M.G., Alexandrov A.A., Serazhim A.A. Results of one-year preventive intervention against cardiovascular risk factors in first-year students. Russian Journal of Preventive Medicine and Public Health. 2017;20(5):47–53. DOI: 10.17116/profmed201720547-53
4. Joint committee for guideline revision. 2016 Chinese guidelines for the management of dyslipidemia in adults. Journal of Geriatric Cardiology. 2018;15(1):1–29. DOI: 10.11909/j.issn.1671-5411.2018.01.011
5. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Revista Espanola De Cardiologia (English Ed.). 2017;70(2):115. DOI: 10.1016/j.rec.2017.01.002
6. Lu X, Liu J, Hou F, Liu Z, Cao X, Seo H et al. Cholesterol induces pancreatic β cell apoptosis through oxidative stress pathway. Cell Stress and Chaperones. 2011;16(5):539–48. DOI: 10.1007/s12192-011-0265-7
7. Li Z-Y, Wang P, Miao C-Y. Adipokines in inflammation, insulin resistance and cardiovascular disease. Clinical and Experimental Pharmacology and Physiology. 2011;38(12):888–96. DOI: 10.1111/j.1440-1681.2011.05602.x
8. Ahima RS, Flier JS. Leptin. Annual Review of Physiology. 2000;62(1):413–37. DOI: 10.1146/annurev.physiol.62.1.413
9. Van Dielen F, van’t Veer C, Schols A, Soeters P, Buurman W, Greve J. Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individuals. International Journal of Obesity. 2001;25(12):1759–66. DOI: 10.1038/sj.ijo.0801825
10. Yamagishi S, Edelstein D, Du X, Kaneda Y, Guzman M, Brownlee M. Leptin Induces Mitochondrial Superoxide Production and Monocyte Chemoattractant Protein-1 Expression in Aortic Endothelial Cells by Increasing Fatty Acid Oxidation via Protein Kinase A. Journal of Biological Chemistry. 2001;276(27):25096–100. DOI: 10.1074/jbc.M007383200
11. Cooke JP, Oka RK. Does Leptin Cause Vascular Disease? Circulation. 2002;106(15):1904–5. DOI: 10.1161/01.CIR.0000036864.14101.1B
12. Konstantinides S, Schafer K, Koschnick S, Loskutoff DJ. Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. Journal of Clinical Investigation. 2001;108(10):1533–40. DOI: 10.1172/JCI13143
13. O’Rourke L, Gronning LM, Yeaman SJ, Shepherd PR. Glucosedependent Regulation of Cholesterol Ester Metabolism in Macrophages by Insulin and Leptin. Journal of Biological Chemistry. 2002;277(45):42557–62. DOI: 10.1074/jbc.M202151200
14. Minokoshi Y, Kim Y-B, Peroni OD, Fryer LGD, Muller C, Carling D et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002;415(6869):339–43. DOI: 10.1038/415339a
15. Filkova M, Haluzik M, Gay S, Senolt L. The role of resistin as a regulator of inflammation: Implications for various human pathologies. Clinical Immunology. 2009;133(2):157–70. DOI: 10.1016/j.clim.2009.07.013
16. Jamaluddin MS, Yan S, Lu J, Liang Z, Yao Q, Chen C. Resistin Increases Monolayer Permeability of Human Coronary Artery Endothelial Cells. PLoS ONE. 2013;8(12):e84576. DOI: 10.1371/journal.pone.0084576
17. Libby P, Ridker PM, Hansson GK. Inflammation in Atherosclerosis: from pathophysiology to practice. Journal of the American College of Cardiology. 2009;54(23):2129–38. DOI: 10.1016/j.jacc.2009.09.009
18. Jialal I, Devaraj S, Adams-Huet B, Chen X, Kaur H. Increased Cellular and Circulating Biomarkers of Oxidative Stress in Nascent Metabolic Syndrome. The Journal of Clinical Endocrinology & Metabolism. 2012;97(10):E1844–50. DOI: 10.1210/jc.2012-2498
19. De Nardo D, Latz E. NLRP3 inflammasomes link inflammation and metabolic disease. Trends in Immunology. 2011;32(8):373–9. DOI: 10.1016/j.it.2011.05.004
20. Malo E, Ukkola O, Jokela M, Moilanen L, Kahonen M, Nieminen MS et al. Resistin Is an Indicator of the Metabolic Syndrome According to Five Different Definitions in the Finnish Health 2000 Survey. Metabolic Syndrome and Related Disorders. 2011;9(3):203–10. DOI: 10.1089/met.2010.0106
21. Zakovryashina I.N., Khaisheva L.A., Shlyk S.V. Study of resistin level and lipid profile in patients with ST-segment elevation due myocardial infarction, results of one-year follow-up. Atherosclerosis and Dyslipidemias. 2021;4(45):51–8. DOI: 10.34687/2219-8202.JAD.2021.04.0006
22. Abate N, Sallam H, Rizzo M, Nikolic D, Obradovic M, Bjelogrlic P et al. Resistin: An Inflammatory Cytokine. Role in Cardiovascular Diseases, Diabetes and the Metabolic Syndrome. Current Pharmaceutical Design. 2014;20(31):4961–9. DOI: 10.2174/1381612819666131206103102
23. Vazquez MJ, Gonzalez CR, Varela L, Lage R, Tovar S, Sangiao-Alvarellos S et al. Central Resistin Regulates Hypothalamic and Peripheral Lipid Metabolism in a Nutritional-Dependent Fashion. Endocrinology. 2008;149(9):4534–43. DOI: 10.1210/en.2007-1708
24. Singh AK, Tiwari S, Gupta A, Natu SM, Mittal B, Pant AB. Association of Resistin with Metabolic Syndrome in Indian Subjects. Metabolic Syndrome and Related Disorders. 2012;10(4):286–91. DOI: 10.1089/met.2011.0128
25. Oh KW, Lee WY, Rhee EJ, Baek KH, Yoon KH, Kang MI et al. The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clinical Endocrinology. 2005;63(2):131–8. DOI: 10.1111/j.1365-2265.2005.02312.x
26. Owecki M, Nikisch E, Miczke A, Pupek-Musialik D, Sowinski J. Serum resistin is related to plasma HDL cholesterol and inversely correlated with LDL cholesterol in diabetic and obese humans. Neuro Endocrinology Letters. 2010;31(5):673–8. PMID: 21173741
27. Wang Y, Lam KSL, Kraegen EW, Sweeney G, Zhang J, Tso AW et al. Lipocalin-2 Is an Inflammatory Marker Closely Associated with Obesity, Insulin Resistance, and Hyperglycemia in Humans. Clinical Chemistry. 2007;53(1):34–41. DOI: 10.1373/clinchem.2006.075614
28. Wu G, Li H, Zhou M, Fang Q, Bao Y, Xu A et al. Mechanism and clinical evidence of lipocalin-2 and adipocyte fatty acid-binding protein linking obesity and atherosclerosis. Diabetes/Metabolism Research and Reviews. 2014;30(6):447–56. DOI: 10.1002/dmrr.2493
29. Ni J, Ma X, Zhou M, Pan X, Tang J, Hao Y et al. Serum lipocalin-2 levels positively correlate with coronary artery disease and metabolic syndrome. Cardiovascular Diabetology. 2013;12(1):176. DOI: 10.1186/1475-2840-12-176
30. Xiao Y, Xu A, Hui X, Zhou P, Li X, Zhong H et al. Circulating Lipocalin-2 and Retinol-Binding Protein 4 Are Associated with Intima-Media Thickness and Subclinical Atherosclerosis in Patients with Type 2 Diabetes. PLoS ONE. 2013;8(6):e66607. DOI: 10.1371/journal.pone.0066607
31. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J et al. Identification of Neutrophil Gelatinase-Associated Lipocalin as a Novel Early Urinary Biomarker for Ischemic Renal Injury. Journal of the American Society of Nephrology. 2003;14(10):2534–43. DOI: 10.1097/01.ASN.0000088027.54400.C6
32. de Carvalho JAM, Tatsch E, Hausen BS, Bollick YS, Moretto MB, Duarte T et al. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as indicators of tubular damage in normoalbuminuric patients with type 2 diabetes. Clinical Biochemistry. 2016;49(3):232–6. DOI: 10.1016/j.clinbiochem.2015.10.016
33. Ibragimov V.M.-E., Sarvilina I.V., Batyushin M.M., Aliskandiev A.M. On the role of lipocalin-2 protein in the progression of diabetic nephropathy and evaluation of the effectiveness of cytoflavin therapy in type-2 diabetes mellitus. Experimental and clinical pharmacology. 2020;83(3):15–22. DOI: 10.30906/0869-2092-2020-83-3-15-22
34. Seino Y, Yabe D. Glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1: Incretin actions beyond the pancreas. Journal of Diabetes Investigation. 2013;4(2):108–30. DOI: 10.1111/jdi.12065
35. Holst JJ, Knop FK, Vilsboll T, Krarup T, Madsbad S. Loss of Incretin Effect Is a Specific, Important, and Early Characteristic of Type 2 Diabetes. Diabetes Care. 2011;34(Suppl 2):S251–7. DOI: 10.2337/dc11-s227
36. Wang X-L, Ye F, Li J, Zhu L-Y, Feng G, Chang X-Y et al. Impaired secretion of glucagon-like peptide 1 during oral glucose tolerance test in patients with newly diagnosed type 2 diabetes mellitus. Saudi Medical Journal. 2016;37(1):48–54. DOI: 10.15537/smj.2016.1.12035
37. Holst JJ. The Physiology of Glucagon-like Peptide 1. Physiological Reviews. 2007;87(4):1409–39. DOI: 10.1152/physrev.00034.2006
38. Nawaz SS, Siddiqui K. Plasminogen activator inhibitor-1 mediate downregulation of adiponectin in type 2 diabetes patients with metabolic syndrome. Cytokine: X. 2022;4(1):100064. DOI: 10.1016/j.cytox.2022.100064
39. Skurk T, Hauner H. Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. International Journal of Obesity. 2004;28(11):1357–64. DOI: 10.1038/sj.ijo.0802778
40. Aso Y. Plasminogen activator inhibitor (PAI)-1 in vascular inflammation and thrombosis. Frontiers in Bioscience. 2007;1(12):2957–66. DOI: 10.2741/2285
Review
For citations:
Kashtanova Е.V., Polonskaya Y.V., Shramko V.S., Shcherbakova L.V., Stakhneva Е.М., Sadovski E.V., Spiridonov A.N., Ragino Yu.I. Associations of adipokines and metabolic hormones with low-density lipoprotein hypercholesterolemia in men and women under 45 years of age. Kardiologiia. 2022;62(11):63-70. https://doi.org/10.18087/cardio.2022.11.n2239