Association of Adiponectin and Leptin Levels with Endothelial Dysfunction in Patients with Metabolic Syndrome: A Cross-Sectional Clinical Study: Adipokines and Endothelial Dysfunction in MetS

Ifra  Ahsan; Muhammad  Mohsin; Muhammad Faizan Saeed  Malik; Naeem  Shahzad

doi:10.69750/dmls.02.08.0146

Authors

Ifra Ahsan Demonstrator, Department of Biochemistry, FMH College of Medicine and Dentistry, Lahore, Pakistan Author
Muhammad Mohsin Demonstrator, Department of Anatomy, Queens Medical College, Kasur, Pakistan. Author
Muhammad Faizan Saeed Malik Demonstrator, Department of Anatomy, Queens Medical College, Kasur, Pakistan. Author
Naeem Shahzad Assistant Professor, Department of Anatomy, M. Islam Medical and Dental College, Gujranwala Author

DOI:

https://doi.org/10.69750/dmls.02.08.0146

Keywords:

Adiponectin, Leptin, Metabolic Syndrome, Endothelial Dysfunction, Flow-Mediated Dilation

Abstract

Background: Metabolic syndrome (MetS) is defined by a group of cardiometabolic disorders such as central obesity, insulin resistance, dyslipidemia, and hypertension, all of which lead to an increased cardiovascular risk. One early indicator of vascular injury in MetS is endothelial dysfunction. Two important adipokines released by adipose tissue, adiponectin and leptin, may affect endothelial function via pro- and anti-inflammatory pathways, respectively.

Objective: To assess the association between circulating adiponectin and leptin levels and endothelial dysfunction in adult patients diagnosed with metabolic syndrome.

Methods: This cross-sectional research was carried out between January 2024 and April 2025 at two tertiary care institutions in Pakistan. There were one hundred individuals with metabolic syndrome in all. Adiponectin and leptin levels in blood were measured using ELISA, and endothelial function was evaluated using flow-mediated dilatation (FMD) of the brachial artery. Endothelial dysfunction was indicated by a flow-mediated dilatation (FMD) of less than 6%. Associations were found using statistical techniques such as t-tests, Pearson's correlation, and multivariate regression.

Results: Patients exhibiting endothelial dysfunction (64%) had markedly reduced adiponectin levels (3.8 ± 1.1 μg/mL) and elevated leptin levels (24.7 ± 5.1 ng/mL) in comparison to those with normal endothelial function. Adiponectin had a favorable association with FMD (r = 0.54, p < 0.001), but leptin showed a significant negative correlation (r = -0.48, p < 0.001). Both adipokines continued to serve as independent predictors of endothelial function after adjustments for metabolic variables.

Conclusion: Adiponectin insufficiency and hyperleptinemia are significantly correlated with compromised endothelial function in metabolic syndrome. These adipokines may function as early indicators and therapeutic targets for the mitigation of cardiovascular risk.

Downloads

Download data is not yet available.

References

Grundy SM. Metabolic syndrome update. Trends Cardiovasc Med. 2016;26(4):364–373. doi:10.1016/j.tcm.2015.10.004

Alberti KG, Zimmet P, Shaw J. Metabolic syndrome—a new world-wide definition. A consensus statement from the IDF. Diabet Med. 2006;23(5):469–480. doi:10.1111/j.1464-5491.2006.01858.x

Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85–97. doi:10.1038/nri2921

Matsuzawa Y. Adiponectin: a key player in obesity-related disorders. Curr Pharm Des. 2010;16(17):1896–1901. doi:10.2174/138161210791164004

Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26(3):439–451. doi:10.1210/er.2005-0005

Karastergiou K, Mohamed-Ali V. The autocrine and paracrine roles of leptin and adiponectin in white adipose tissue. J Clin Endocrinol Metab. 2010;95(6):2402–2410. doi:10.1210/jc.2009-2070

Vaverkova H, Kuthanova L, Borucka J, Halenka M, Karasek D. Adiponectin, leptin and endothelial dysfunction in patients with metabolic syndrome. Physiol Res. 2020;69(4):671–682. doi:10.33549/physiolres.934358

Schinzari F, Tesauro M, Rovella V, et al. Leptin and vascular function: facts and perspectives. Curr Hypertens Rep. 2017;19(12):54. doi:10.1007/s11906-017-0768-4

Frühbeck G, Catalán V, Rodríguez A, Gómez-Ambrosi J. Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk. Adipocyte. 2018;7(1):57–62. doi:10.1080/21623945.2018.1457039

Yamauchi T, Kadowaki T. Adiponectin receptor as a key player in healthy longevity and obesity-related diseases. Cell Metab. 2013;17(2):185–196. doi:10.1016/j.cmet.2013.01.001

Ghantous CM, Azrak Z, Hanache S, Abou-Kheir W, Zeidan A. Differential role of leptin and adiponectin in cardiovascular system. Int J Endocrinol. 2015;2015:534320. doi:10.1155/2015/534320

Ruan H, Lodish HF. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev. 2003;14(5):447–455. doi:10.1016/S1359-6101(03)00052-2

Muniyappa R, Montagnani M, Koh KK, Quon MJ. Cardiovascular actions of insulin. Endocr Rev. 2007;28(5):463–491. doi:10.1210/er.2007-0006

Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014;371(12):1131–1141. doi:10.1056/NEJMra1011035

Yoon MJ, Lee GY, Chung JJ, Ahn YH, Hong SH, Kim JB. Adiponectin increases fatty acid oxidation in skeletal muscle cells. Mol Cell Biol. 2006;26(2):773–782. doi:10.1128/MCB.26.2.773-782.2006

Misra A, Khurana L. The metabolic syndrome in South Asians: epidemiology, determinants, and prevention. Metab Syndr Relat Disord. 2009;7(6):497–514. doi:10.1089/met.2009.0024

Lear SA, Humphries KH, Kohli S, Chockalingam A, Frohlich JJ, Birmingham CL. Visceral adipose tissue accumulation differs across the BMI spectrum. J Am Coll Cardiol. 2007;49(8):903–910. doi:10.1016/j.jacc.2006.10.056

Singh S, Deepa M, Grace M, et al. Prevalence of metabolic syndrome and its association with adipokines in urban South Indian population. Metab Syndr Relat Disord. 2021;19(4):214–221. doi:10.1089/met.2020.0081

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/BF03401386

Santos SHS, Andrade JM. Metabolic effects of adiponectin and leptin on the cardiovascular system. Horm Mol Biol Clin Investig. 2017;31(2):1–9. doi:10.1515/hmbci-2016-0061

Li CJ, Li J, Zhang QT, et al. GLP-1 receptor agonists and cardiovascular protection: current status and future perspectives. Front Pharmacol. 2021;12:730911. doi:10.3389/fphar.2021.730911

Chan DC, Watts GF, Barrett PH, Burke V. Effects of fenofibrate and atorvastatin on markers of inflammation and endothelial function. Atherosclerosis. 2002;162(2):297–304. doi:10.1016/S0021-9150(01)00684-1

Hivert MF, Sullivan LM, Fox CS, et al. Associations of adiponectin, resistin, and TNF-alpha with insulin resistance. J Clin Endocrinol Metab. 2008;93(8):3165–3172. doi:10.1210/jc.2008-0135

Hansel B, Giral P, Nobecourt E, et al. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense HDL. Arterioscler Thromb Vasc Biol. 2004;24(4):877–882. doi:10.1161/01.ATV.0000120382.23278.38

Heidemann C, Sun Q, van Dam RM, Meigs JB, Zhang C, Tworoger SS, et al. Adiponectin and risk of type 2 diabetes in women. Diabetes Care. 2008;31(2):231–236. doi:10.2337/dc07-1531