International Journal of Drug Delivery Technology
Volume 14, Issue 1

A Review on the Evaluation of Serum Adipokine (adiponectin, leptin) Levels in Cardiovascular Disease: A Systemic Review

Kainaat Khan1*, Tariq Mahmood1, Alok Singhal2, Shalabh Agarwal2, Sangeeta Kapoor1

1Department of Biochemistry, Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India.

2Department of Medicine, Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India. 

Received: 26th December, 2023; Revised: 15th January, 2024; Accepted: 20th February, 2024; Available Online: 25th March, 2024

ABSTRACT

Background: This review enumerates current knowledge of adipose tissue and reveals processes by which adipocytes affect obesity and cardiovascular illness. Obesity, according to growing evidence, is a crucial factor that influences cardiometabolic phenotypes. However, the pathogenic mechanisms are still unknown. As per recent reports, adipose tissue interacts with a variety of organs, including the lungs, heart, and kidneys, by secreting multiple cytokines known as adipokines.

Aim and Objectives: The current study examines the adipokine (adiponectin and leptin) profiles of adipocytes from the

adipose tissue and biochemical and clinical parameters in patients with heart disease (CVD).

Methods: Relevant articles were retrieved by screening the following databases: Medline (PubMed, Scopus), Web of Science. Keyword searches included ‘adiponectin’, ‘leptin’, AND ‘cardiovascular disease’, from 2013-2023 (May). The retrieved studies were subjected through a screening procedure to identify case-control, cohort and epidemiological studies that contained the required data. Per preferred reporting items for systematic reviews and (PRISMA) guidelines, we conducted the systematic review.

Results: A total of 2377 studies were found relevant, out of which only 90 fulfilled the inclusion criteria. From these 90 studies

we reviewed 50 articles that are included in the systematic review.

Conclusion: The dysfunction of adipose tissue triggered an alteration in the secretory profile of adipokines, which serves as a signal of metabolic disorder. An imbalance in pro- and anti-inflammatory adipokine formation exacerbates cardiometabolic diseases and CVD challenges.

Keywords: Adipokines, Adiponectin, Cardiovascular disease, Leptin, Obesity

Highlights

to find the effect of these adipokines in inflammation and different cardiovascular aetiologies.

International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.1.75

How to cite this article: Khan K, Mahmood T, Singhal A, Agarwal S, Kapoor S. A Review on the Evaluation of Serum Adipokine (adiponectin, leptin) Levels in Cardiovascular Disease: A Systemic Review. International Journal of Drug Delivery Technology. 2024;14(1):545-555.

REFERENCES

  1. Steven S, Frenis K, Oelze M, Kalinovic S, Kuntic M, Bayo Jimenez MT, et al. Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease. Oxid Med Cell Longev. 2019;2019:7092151.
  2. Xu A, Vanhoutte PM. Adiponectin and adipocyte fatty acid binding protein in thepathogenesis of cardiovascular disease. Am J Physiol-Heart Circ Physiol. 2012;302(6):H1231–40.
  3. Nakamura K, Fuster JJ, Walsh Adipokines: a link between obesity and cardiovasculardisease. J Cardiol. 2014;63(4):250–9.
  4. Katsiki N, Mikhailidis DP, Banach M. Leptin, cardiovascular diseases and type 2 diabetes Acta Pharmacol Sin. 2018;39(7):1176–88.
  5. Stewart J, Manmathan G, Wilkinson P. Primary prevention of cardiovascular disease: Areview of contemporary guidance and literature. JRSM Cardiovasc Dis. 2017;6:2048004016687211.
  6. Ha EE, Bauer RC. Emerging Roles for Adipose Tissue in Cardiovascular Disease. Arterioscler Thromb Vasc Biol [Internet]. 2018 Aug [cited 2023 June 14];38(8). Availablefrom: https://ahajournals.org/doi/10.1161/ATVBAHA.118.311421
  7. Smekal A, Vaclavik Adipokines and cardiovascular disease: A comprehensive review.Biomed Pap. 2017;161(1):31–40.
  8. Zhao S, Kusminski CM, Scherer PE. Adiponectin, Leptin and Cardiovascular Disorders.Circ Res. 2021;128(1):136–49.
  9. Ghantous CM, Azrak Z, Hanache S, Abou-Kheir W, Zeidan A. Differential Role of Leptin and Adiponectin in Cardiovascular System. Int J Endocrinol. 2015;2015:1–13.
  10. Lekva T, Michelsen AE, Aukrust P, Henriksen T, Bollerslev J, Ueland Leptin andadiponectin as predictors of cardiovascular risk after gestational diabetes mellitus. Cardiovasc Diabetol. 2017;16(1):5.
  11. Adipokines as novel biomarkers and regulators of the metabolic syndrome - PMC[Internet]. [cited 2023 June 14].
  12. Kim-Mitsuyama S, Soejima H, Yasuda O, Node K, Jinnouchi H, Yamamoto E, et al. Total adiponectin is associated with incident cardiovascular and renal events in treated hypertensive patients: subanalysis of the ATTEMPT-CVD randomized trial. Sci Rep. 2019;9(1):16589. doi: 10.1038/s41598-019-52977-x. PMID: 31719604
  13. Tu WJ, Qiu HC, Liu YK, Liu Q, Zeng X, Zhao Elevated levels of adiponectin associated with major adverse cardiovascular and cerebrovascular events and mortality risk in ischemic stroke. Cardiovasc Diabetol. 2020;19(1):125.
  14. Ruijter HM, Pasterkamp G, Jager Adiponectin Regulation in Cardiovascular Disease is Diseased Fat Showing Its True Color? Arterioscler Thromb Vasc Biol. 2014;34:2180-2181.
  15. Mazloum Khorasani Z, Choobkar S, Khameneh Bagheri R, AkbariRad M, Firoozi The Relationship Between Adiponectin Serum Level and Coronary Artery Disease in Type 2 Diabetic Patients. Acta Med Iran. 2021;59(3):142-147.
  16. Ja Young Jeon, Kyoung Hwa Ha, Seung Jin Han, Hae Jin Kim, Kwan-Woo Lee and Dae Jung Kim. Blood adiponectin levels are not associated with risk of cardiovascular events in patients with type 2 diabetes. Diabetes & Vascular Disease Research 2018;15(6):571–575.
  17. Nomura H, Arashi H, Yamaguchi J, Ogawa H, Hagiwara N. Relation of Adiponectin to Cardiovascular Events and Mortality in Patients With Acute Coronary Syndrome. Am J Cardiol. 2021;140:7-12. doi: 10.1016/j.amjcard.2020.10.053. Epub 2020 Nov 2. PMID: 33144157
  18. Mukama T, Johnson T, Kaaks R et al. Effect modification by NT-proBNP on the association between adiponectin and total mortality in EPIC–Heidelberg: A case-cohort study, 25 May 2022, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1669374/v1]
  19. Zaidi H, Byrkjeland R, Idau N, Åkra S , Solheim S, Arnesen H, et al. Opstad.Adiponectin in relation to exercise and physical performance in patients with type 2 diabetes and coronary artery disease, Adipocyte, 2021;10:(1)612-20, DOI: 1080/21623945.2021.1996699.
  20. Persson J, Strawbridge RJ, McLeod O, Gertow K, Silveira A, Baldassarre D, IMPROVE Study Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease. J Am Heart Assoc. 2015;4(8):e001853. doi: 10.1161/JAHA.115.001853. PMID: 26276317; PMCID: PMC4599454.
  21. Zhang, YQ, Zhang, YW., Dai, JL. et al. Serum CTRP9 and high-molecular weight adiponectin are associated with ischemic stroke. BMC Neurol 2022;22(3):429.
  22. Zhang HL and Jin X. Relationship between serum adiponectin and osteoprotegerin levels and coronary heart disease severity. Genetics and Molecular Research. 2015;14(3): 11023-11029.
  23. Xia K, Guo L, Zhao Z, Md Sayed AS, Li F, Yang Plasma level of adiponectin in coronary heart disease patients combined with abnormal glucose metabolism Chinese. 2012;37(2):179-84. doi: 10.3969/j.issn.1672-7347.2012.02.012. PMID: 22561436.
  24. Matsushita, Y, Nakagawa T, Yamamoto S, Kato T, Ouchi T, Kikuchi N, et al. Adiponectin and visceral fat associate with cardiovascular risk Obesity, 2014;22(5): 287-291. https:// doi.org/10.1002/oby.20425
  25. Schrieks IC, Nozza A, Stähli BE, Buse JB, Henry RR, Malmberg K, et al. Adiponectin, Free Fatty Acids, and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Acute Coronary Syndrome. Diabetes Care 2018;41(8):1792–1800. https://doi.org/10.2337/dc18-0158
  26. Ghanbari AA, Dörr R, Spitzer S, Stumpf J, Britz A, Zalan IA, et al. Adiponectin in coronary heart disease and newly diagnosed impaired glucose tolerance. Diabetes & Vascular Disease Research. 2019;10(5):452–458.
  27. Ilic SS, Stojanović S, Petrovic V. Impact of Adiponectin Resistance on Coronary Artery Disease Severity. Nigerian Journal of Clinical Practice. 2021;24(8):1240-6. DOI: 10.4103/ njcp_611_19.
  28. Kerunne SK, Wendy SP, Xiuhong L, Palella, Jr FJ, Lisa PJ, Joseph BM, et al. Lower adiponectin is associated with subclinical cardiovascular disease among HIV-infected men. AIDS 2014;28(6):901-9.| DOI:10.1097/QAD.0000000000000186
  29. Wang Z, Li B, Wang Y. et al. The association between serum adiponectin and 3-month outcome after ischemic stroke. Cardiovasc Diabetol. 2019;18(3):105. https://doi.org/10.1186/ s12933-019-0908-z.
  30. Wang G, Wang Y, Luo Effect of Adiponectin Variant on Lipid Profile and Plasma Adiponectin Levels: A Multicenter Systematic Review and MetaAnalysis. Cardiovascular therapeutics 2022;12(5):1-18.
  31. Vavruch C, Länne T, Fredrikson, et al. Serum leptin levels are independently related to the incidence of ischemic heart disease in a prospective study of patients with type 2 diabetes. Cardiovasc Diabetol. 2015;14:62. https://doi.org/10.1186/s12933-015-0208-1V
  32. Nalini D, Karthick R, Shirin V. et al. “Role of the adipocyte hormone leptin in cardiovascular diseases – a study from Chennai based Population”. Thrombosis J. 2015;13:12. https:// org/10.1186/s12959-015-0042-4
  33. Saber H, Himali JJ, Shoamanesh A, Beiser A, Pikula A, Harris TB, et al. Serum Leptin Levels and the Risk of Stroke: The Framingham Study. Stroke. 2015;46(10):2881-5. doi: 10.1161/ 115.009463. PMID: 26337973; PMCID: PMC4589501.
  34. Yang H, Guo W, Li J, Cao S, Zhang J, Pan J, et al. Leptin concentration and r isk of coronary heart disease and stroke: A systematic review and meta-analysis. PLoS One. 2017;9;12(3):e0166360. doi: 10.1371/journal.pone.0166360. PMID:28278178; PMCID: PMC5344319.
  35. Ghanizadeh S, Ghaedian T, Firuzyar T, Faghihi A, Taklimi NJ. Evaluating the correlation of serum leptin levels with evidence of coronary artery disease on myocardial perfusion single-photon emission computed tomography in suspected coronary artery disease Nucl Med Commun. 2022 ;43(3):265-269. doi: 10.1097/MNM.0000000000001512. PMID: 34908021.
  36. Chen J, Xie Z, Bin Z. The Association Between Serum Leptin Levels and Cardiovascular Events in Patients with Rheumatoid Arthritis. Lab Med. 2021;52(1):86-92. doi: 10.1093/labmed/ lmaa037. PMID: 32754755.
  37. Lai YH, Wang CH, Tsai JP, Hou JS, Lee CJ, Hsu High serum leptin level is associated with peripheral artery disease in adult peritoneal dialysis patients. 2018;30(2):85-89. doi: 10.4103/tcmj. tcmj_8_18. PMID: 29875588; PMCID: PMC5968748.
  38. Chiu FH, Chuang CH, Li WC, Weng YM, Fann WC, Lo HY, et The association of leptin and C-reactive protein with the cardiovascular risk factors and metabolic syndrome score in Taiwanese adults. Cardiovasc Diabetol. 2012 ;11:40. doi: 10.1186/1475-2840-11-40. PMID: 22533665; PMCID: PMC3471043.
  39. Hanboly NH, Salama1 S, Gaber M, Marzouk Serum leptin and future cardiovascular events in patients with acute coronary syndrome Departments of 1 Cardiovascular Diseases and 2 Clinical Pathology, Cairo University, Cairo, Egypt 2018;196.147.20.219.
  40. Qin Z, Yang Q, Yang M, Han ,M, Yuqin Xiong, Ruoxi Liao, et Serum leptin concentration can predict cardiovascular outcomes and all-cause death in maintenance hemodialysis patients,Clinica Chimica Acta. 2021;520:87-94.
  41. Liu Y, Gu Y, Shen Y, Lin B, Li Y, XHe, et Association Between Serum Leptin Level and Calcific Aortic Valve Disease. Journal of American Heart Association. 2019;8(9):e012495.
  42. Martin SS, Blaha MJ, Muse ED, Qasim AN, Reilly MP, Blumenthal RS, et al. Leptin and incident cardiovascular disease: the Multi- ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2015;239(1):67-72. doi: 1016/j.atherosclerosis.2014.12.033. Epub 2014 Dec 20. PMID: 25574859; PMCID: PMC4331218.
  43. Christen T, Mutsert RD, Smit RAJ, Dijk WVK, Hildo J, et al.The association between leptin and subclinical cardiovascular disease explained by body fat: Observational and Mendelian randomization analyses,Nutrition, Metabolism and Cardiovascular Diseases. 2023;33(5):1077-1086.
  44. Aljaloud KS, Hughes A R, Galloway Impact of Physical Activity on Adiposity and Risk Markers for Cardiovascular and Metabolic Disease. Am J Mens Health. 2022;16(2):15579883221092289. doi: 10.1177/15579883221092289. PMID: 35466785; PMCID: PMC9036347.
  45. Montazerifar F, Bolouri A, Paghalea RS, Mahani MK, Karajibani Obesity, Serum Resistin and Leptin Levels Linked to Coronary Artery Disease. Arq Bras Cardiol. 2016;107(4):348-353. doi: 10.5935/abc.20160134. Epub 2016 Sep 12. PMID: 27627223; PMCID: PMC5102481.
  46. Zonneveld MH, Noordam R, Grond JVD, Heemst DV, Mooijaart SP, Sabayan B, et Trompet, Interplay of circulating leptin and obesity in cognition and cerebral volumes in older adults,Peptides. 2021;135:170424.
  47. Caffo O, Ralston PA, Lemacks JL, Young-Clark I, Wickrama KKAS, Ilich Sex and Body Circumferences Associated with Serum Leptin in African American Adults. J Womens Health (Larchmt). 2021;30(12):1769-1777. doi: 10.1089/jwh.2020.8820. PMID: 33661054; PMCID: PMC8721506.
  48. Wang H, Wang C, Han W, Geng C, Chen D, Wu B, et al. Association of leptin and leptin receptor polymorphisms with coronary artery disease in a North Chinese Han Rev Soc Bras Med Trop. 2020;53:e20190388. doi: 10.1590/0037-8682- 0388-2019. PMID: 32049202; PMCID: PMC7083392
  49. Yan H, Yu B, Tian J, Xia D, Xu Y, Li C. Serum Leptin and Adiponectin: Indicators of Cardiovascular Disease Secondary to Indian J Dermatol. 2022;67(2):109-114. doi: 10.4103/ijd. ijd_927_21. PMID: 36092186; PMCID: PMC9455115.
  50. Anaszewicz M, Wawrzeńczyk A, Czerniak B, Banaś W, Socha E, Lis K, et Leptin, adiponectin, tumor necrosis factor α, and irisin concentrations as factors linking obesity with the risk of atrial fibrillation among inpatients with cardiovascular diseases. Kardiol Pol. 2019;77(11):1055-1061. doi: 10.33963/KP.14989. Epub 2019 Sep 25. PMID: 31553329.
  51. Larsen MA, Isaksen VT, Moen OS, Wilsgaard L, Remijn M, Paulssen EJ, et al. Leptin to adiponectin ratio - A surrogate biomarker for early detection of metabolic disturbances in Nutr Metab Cardiovasc Dis. 2018;28(11):1114-1121. doi: 10.1016/j.numecd.2018.06.020. Epub 2018 Jul 3. PMID: 30145019.
  52. Zhao S, Kusminski CM, Scherer PE. Adiponectin, Leptin and Cardiovascular Disorders. Circ Res. 2021;128(1):136-149. doi: 1161/CIRCRESAHA.120.314458. PMID: 33411633; PMCID: PMC7799441.
  53. Lee JY, Bak JK, Kim M, Shin HG, Park KI, Lee SP, et Long- term cardiovascular events in hypertensive patients: full report of the Korean Hypertension Cohort. Korean J Intern Med. 2023;38(1):56-67. doi: 10.3904/kjim.2022.249. PMID: 36514267; PMCID: PMC9816676.
  54. Rahmani A, Toloueitabar Y, Mohsenzadeh Y, Hemmati R, Sayehmiri K, Asadollahi Association between plasma leptin/ adiponectin ratios with the extent and severity of coronary artery disease. BMC Cardiovasc Disord. 2020 Nov 4;20(1):474. doi: 10.1186/s12872-020-01723-7. PMID: 33148166; PMCID: PMC7640417
  55. Kajikawa Y, Ikeda M, Takemoto S, Tomoda J, Ohmaru N, Kusachi Association of circulating levels of leptin and adiponectin with metabolic syndrome and coronary heart disease in patients with various coronary risk factors. Int Heart J. 2011;52(1):17-22. doi: 10.1536/ihj.52.17. PMID: 21321463.
  56. Bidulescu A, Liu J, Chen Z, Hickson DA, Musani SK, Samdarshi TE, et al. Associations of adiponectin and leptin with incident coronary heart disease and ischemic stroke in african americans: the jackson heart Front Public Health. 2013;1:16. doi: 10.3389/fpubh.2013.00016. PMID: 24350185; PMCID: PMC3854845
  57. Rostoff P, Siniarski A, Haberka M, Konduracka M, Nessler J, GGajos. Relationship among the leptin-to-adiponectin ratio, systemic inflammation, and anisocytosis in well-controlled type 2 diabetic patients with atherosclerotic cardiovascular Kardiol Pol 2020;78(5):420-428.DOI: 10.33963/KP.15257Pubmed: 32210218
  58. Rose SAE, Mitchell EJM, Khoudary RE, Huang HH, Wang Q, Imke Janssen. Adipokines and Subclinical Cardiovascular Disease in Post‐Menopausal Women: Study of Women’s Health Across the Nation. J Am Heart Assoc. 2021;10(7):e019173.
  59. Sawaguchi T, Nakajima T , Haruyama A, Hasegawa T, Shibasaki I, Nakajima T, et Association of serum leptin and adiponectin concentrations with echocardiographic parameters and pathophysiological states in patients with cardiovascular disease receiving cardiovascular surgery. PLOS ONE 14(11): e0225008.
  60. Toulis KA, Jiang CQ, Hemming K, Nirantharakumar K, Cheng KK, et al. (2018) Discriminatory performance of adiponectin and leptin in the identification of impaired glucose tolerance: The Guangzhou Biobank Cohort Study - Cardiovascular Disease PLOS ONE 13(11): e0206964. https://doi.org/10.1371/ journal.pone.0206964
  61. Seven E, Husemoen LLN, Sehested TSG, Ibsen H, Wachtell K, et al. (2015) Adipocytokines, C-Reactive Protein, and Cardiovascular Disease: A Population-Based Prospective PLOS ONE 10(6): e0128987. https://doi.org/10.1371/journal. pone.0128987.