Visceral adipose tissue according to magnetic resonance imaging as a factor associated with leptin resistance in stable coronary artery disease

Aim. To evaluate quantitative and radiomic characteristics of abdominal vis­ceral adipose tissue (VAT) using magnetic resonance imaging (MRI), their relationship with lipid, carbohydrate metabolism, inflammation in pa­tients with coronary artery disease (CAD), as well as the association of these factors with leptin resistance (LR).

Material and methods. The study included 46 patients with stable CAD. MRI was performed to determine the volume (cm3) of abdominal adi­pose tis­sue. The serum levels of glucose and insulin, lipid profile, proinflam­ma­to­ry markers and adipokines were determined. For quantitative asses­sment of LR, the free leptin index (FLI) was calculated (FLI >25 indicates LR).

Results. In the group with LR, body mass index and homeostasis mo­del assessment of insulin resistance (HOMA-IR), the levels of insu­lin, adipo­nec­tin, leptin and FLI were significantly higher, while the adipo­nectin/leptin ratio and the blood level of leptin receptors were lower than in the group of patients without LR. No intergroup differences in abdominal fat volume were found. The group with LR was characterized by a significantly lower value of such radiomic characteristics as Entropy and Variance. The fol­lowing factors associated with LR were included in the multivariate logistic regression analysis model: age (odds ratio (OR) 1,24, 95% confidence interval (CI): 1,05-1,47), glucose level (OR 2,50, 95% CI: 0,73-8,62), soluble leptin receptor level (OR 0,65, 95% CI: 0,47-0,91), smoking (OR 0,43, 95% CI: 0,065-2,89) and Entropy (OR 2,44, 95% CI: 0,13-46,5). The sensitivity and specificity of the model are 90,6 and 57,1%, respectively.

Conclusion. Significant factors associated with LR in patients with stable CAD were identified: Entropy, older age, high glucose levels, smoking, and low levels of soluble leptin receptors.

1. Borodkina AD, Gruzdeva OV, Akbasheva OE, et al. Leptin resis­tance: unsolved diagnostic issues. Problems of Endocrinology. 2018;64(1):62-6. (In Russ.) doi:10.14341/probl8740.

2. Dedov II, Mokrysheva NG, Mel’nichenko GA, et al. Obesity. Cli­nical guidelines. Consilium Medicum. 2021;23(4):311-25. (In Russ.) doi:10.26442/20751753.2021.4.200832.

3. Zhao Sh, Kusminski CM, Elmquist JK, et al. Leptin: Less Is More. Diabetes. 2020;69(5):823-9. doi:10.2337/dbi19-0018.

4. Izquierdo AG, Crujeiras AB, Casanueva FF, et al. Leptin, obesity, and leptin resistance: Where are we 25 years later? Nutrients. 2019;11(11):2704. doi:10.3390/nu11112704.

5. Machann J, Stefan N, Wagner R, et al. Normalized Indices Derived from Visceral Adipose Mass Assessed by Magnetic Re­sonance Ima­ging and Their Correlation with Markers for Insulin Re­sistance and Pre­diabetes. Nutrients. 2020;12(7):2064. doi:10.3390/nu12072064.

6. Vita E, Stefani A, Piro G, et al. Leptin-­mediated meta-inflam­mation may provide survival benefit in patients receiving maintenance immunotherapy for extensive-­stage small cell lung cancer (ES-SCLC). Cancer Immunol Immunother. 2023;72(11): 3803-12. doi:10.1007/s00262-023-03533-0.

7. Podzolkov VI, Bragina AE, Rodionova YuN, et al. Ectopic adi­pose tissue: frequency and clinical characteristics of obesity phenotypes in patients. Cardiovascular Therapy and Prevention. 2024;23(6):3980. (In Russ.) doi:10.15829/1728-8800-2024-3980.

8. Zyubanova IV, Ryumshina NI, Mordovin VF, et al. Relationships of the size of abdominal and perirenal fat depots with markers of meta-inflammatory and renal damage in patients with resistant hypertension. Arterial’naya Gipertenziya = Arterial Hypertension. 2024;30(2):207-23. (In Russ.) doi:10.18705/1607-419X-2024-2318.

9. Tharmaseelan H, Froelich MF, Nörenberg D, et al. Influence of local aortic calcification on periaortic adipose tissue radiomics texture features-a primary analysis on PCCT. Int J Cardiovasc Ima­ging. 2022;38(11):2459-67. doi:10.1007/s10554-022-02656-2.

10. Gavrilova NE, Metelskaya VA, Perova NV, et al. Selection for the quantitative evaluation method of coronary arteries based upon comparative analysis of angiographic scales. Russian Journal of Cardiology. 2014;(6):24-9. (In Russ.)

11. Gorbatovskaya EE, Dyleva YuA, Belik EV, et al. Identification of leptin resistance in patients with coronary artery disease and heart defects. Russian Journal of Cardiology. 2023;28(8):5455. (In Russ.) doi:10.15829/1560-4071-2023-5455.

12. Brown RJ, Meehan CA, Gorden P. Leptin does not mediate hy­pertension associated with human obesity. Cell. 2015;162(3): 465-6. doi:10.1016/j.cell.2015.07.007.

13. Gruzdeva O, Uchasova E, Dyleva Y, et al. Adipocytes Directly Affect Coronary Artery Disease Pathogenesis via Induction of Adipokine and Cytokine Imbalances. Front Immunol. 2019; 10:2163. doi:10.3389/fimmu.2019.02163.

14. Polyakova EA. The role of soluble leptin receptor in the patho­genesis of coronary heart disease. Regional blood circu­lation and microcirculation. 2021;20(3):34-45. (In Russ.) doi:10.24884/1682-6655-2021-20-3-34-45.

15. Drapkina OM. Smoking and related problems in the practice of a cardiologist. Arterialnaya gipertenziya. 2010;16(2):164-9. (In Russ.)

16. Hussein YKhH. Leptin and gender characteristics of metabolic disorders in obesity. Juvenis scientia. 2022;8(1):19-31. (In Russ.) doi:10.32415/jscientia_2022_8_1_19-31.

17. Gruzdeva OV, Belik EV, Dyleva YuA, et al. Relationships between the expression of adipocytokine genes and the calcification of coronary arteries in patients with coronary artery disease. The Siberian Journal of Clinical and Experimental Medicine. 2021;36(3):68-77. (In Russ.) doi:10.29001/2073-8552-2021-36-3-68-77.

18. Kern L, Mittenbühler MJ, Vesting AJ, et al. Obesity-­induced TNFα and IL-6 signaling: The missing link between obesity and inflammation-­driven liver and colorectal cancers. Cancers (Basel). 2018;11(1):24-45. doi:10.3390/cancers11010024.

19. Wang M, Luo Y, Cai H, et al. Prediction of type 2 diabetes mel­litus using noninvasive MRI quantitation of visceral abdo­minal adiposity tissue volume. Quant Imaging Med Surg. 2019;9(6):1076-86. doi:10.21037/qims.2019.06.01.

20. Ryumshina NI, Koshelskaya OA, Kologrivova IV, et al. MRI as­sessment of the abdominal adipose tissue and the state of the abdominal aorta in patients with coronary artery disease: as­sociation with metabolic disorders. Bulletin of Siberian Medicine. 2021;20(3):95-104. (In Russ.) doi:10.20538/1682-0363-2021-3-95-104.

21. Genske F, Kühn JP, Pietzner M, et al. Abdominal fat deposits determined by magnetic resonance imaging in relation to leptin and vaspin levels as well as insulin resistance in the general adult population. Int J Obes. 2018;42:183-9. doi:10.1038/ijo.2017.187.

22. Нudiakova AD, Polonskaya YV, Shcherbakova LV, et al. Asso­ciations of circulating adipokines and coronary artery disease in young adults. Cardiovascular Therapy and Prevention. 2024;23(5):3965. (In Russ.) doi:10.15829/1728-8800-2024-3965.

23. Hu GQ, Ge YQ, Hu XK, et al. Predicting coronary artery calcified plaques using perivascular fat CT radiomics features and clinical risk factors. BMC Med Imaging. 2022;22(1):134. doi:10.1186/s12880-022-00858-7.

24. Mundt P, Tharmaseelan H, Hertel A, et al. Periaortic adipose radiomics texture features associated with increased coronary calcium score-­first results on a photon-­counting-­CT. BMC Med Imaging. 2023;23(1):97. doi:10.1186/s12880-023-01058-7.

25. Kahmann J, Tharmaseelan H, Riffel P, et al. Pericoronary ra­diomics texture features associated with hypercholesterolemia on a photon-­counting-­CT. Front Cardiovasc Med. 2023;10:1223035. doi:10.3389/fcvm.2023.1223035.

26. Lin A, Kolossváry M, Yuvaraj J, et al. Myocardial Infarction As­sociates With a Distinct Pericoronary Adipose Tissue Radiomic Phenotype: A Prospective Case-­Control Study. JACC Cardiovasc Imaging. 2020;13(11):2371-83. doi:10.1016/j.jcmg.2020.06.033.

27. Ilyushenkova JN, Sazonova SI, Popov EV, et al. Radiomic pheno­ty­pe of periatrial adipose tissue in the prognosis of late postabla­tion recurrence of idiopathic atrial fibrillation. Sovrem Tekhnologii Med. 2023;15(2):48-58. (In Russ.) doi:10.17691/stm2023.15.2.05.

28. Saleh M, Virarkar M, Mahmoud HS, et al. Radiomics analysis with three-­dimensional and two-dimensional segmentation to predict survival outcomes in pancreatic cancer. World J Radiol. 2023;15(11):304-14. doi:10.4329/wjr.v15.i11.304.

29. Lee MJ, Kim J. The pathophysiology of visceral adipose tissues in cardiometabolic diseases. Biochem Pharmacol. 2024;222: 116116. doi:10.1016/j.bcp.2024.116116.

30. Chen HJ, Yan XY, Sun A, et al. Adipose extracellular matrix deposition is an indicator of obesity and metabolic disorders. J Nutr Biochem. 2023;111:109159. doi:10.1016/j.jnutbio.2022.109159.