INTERRELATION OF ADIPOKINS OF BLOOD WITH MARKERS OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE WITH OVERWEIGHT AND OBESITY

Pivtorak K. V., Shevchuk N. A., Pivtorak N. A.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

The purpose of the study – evaluate the relationship between the level of adipokins, markers of endothelial dysfunction with the degree of obesity, insulin resistance in patients with NAFLD. Object and methods. 195 patients with overweight and obesity were examined, 68 of them were overweight (BMI-25-29.9 kg / m2), 50 were obese of the 1st degree (BMI-30-34.9 kg / m2), 24 – Obesity II degree (BMI-35-39.9 kg / m2) and 53 patients had normal body mass (BMI-18-24.9 kg / m2). Among the surveyed there were 119 women (61.1) and 76 men (38.9%). Also we examined 20 practically healthy people. The level of glucose was assessed by glucose oxidase method, insulin by the immunoassay method in patient on an empty stomach. The presence of insulin resistance was estimated at the level of the HOMA-IR index. All subjects were assigned the level of C-reactive protein, endothelin (ET-1) immunoassay using the “hsCRP ELISA” (“DRG” USA) and “Endothelin-1” (“DRG” USA). The activity of the Villebrand factor (vWF) was determined by the immune enzyme method used by the company “Shield diagnostics”, Great Britain. The level of adipokines (leptin and adiponectin) was determined using “Human Leptin Quantikine ELISA Kit” (RDS, USA), “(BioVendor, Czech Republic) on the Immunoassay Analyzer, FaxStart (USA). The ratio between the content of adiponectin and leptin was represented as a decimal logarithm (log A / L). The statistical analysis of the obtained results was carried out using the STATISTICA 8 program of Statsoft Company using parametric and nonparametric methods for evaluating the obtained results. Results and discussion. Correlation analysis revealed a direct correlation between HOMA-IR and leptin concentration (r = 0.8; p = 0.0000) and inverse correlation relation between HOMA-IR and adiponectin concentration (r = -0.66; p = 0.0000) and index log A / L (r = -0.71; p = 0.0000) It is evident that the decrease in the concentration of adiponectin with a parallel increase in the content of leptin increases IP. A comparative analysis of the level of CRP inflammation marker in obese patients showed a direct relationship with HOMA-IR (r = 0.58; p = 0.0000), glucose (r = 0.44; p = 0.0000) and insulin (r = 0.66; p = 0.0000) in the blood. Conclusions. In patients with NAFLD, overweight and obesity with increasing levels of leptin, the decrease in serum adiponectin levels was associated with an increase in body mass index, insulin resistance, and an increase in CRP concentrations. The development of the disease is associated with the development of endothelial dysfunction (increased concentrations of ET-1 and vWF activity). A direct correlation connection of average strength between the concentrations of ET-1 and CRP is established.

nonalcoholic fatty liver disease, overweight, obesity, adiponectin, leptin, endothelin-1

1. Sayiner M, Koenig A, Henry L, Younossi ZM. Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in the United States and the Rest of the World. Clin Liver Dis 2016 May 20;(2):205-14. PMID: 27063264 DOI: 10.1016/j.cld.2015.10.001
2. Anstee QM, McPherson S, Day CP. How big a problem is non-alcoholic fatty liver disease? BMJ 2011 July 18;343:d3897. PMID: 21768191 DOI: 10.1136 / bmj.d3897
3. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 2003 Dec;112(12):1796-808. PMCID: PMC296995 DOI: 10,1172 / JCI19246
4. Babak OIa, Kolesnikova OV, Shut IV. Vplyv syrovatkovoho rivnia adyponektynu na vyrazhenist nealkoholnoho steatozu pechinky u khvorykh na tsukrovyi diabet 2 typu z nadlyshkovoiu masoiu tila. Suchasna hastroenterolohiia 2011;1(57):5-11. [in Ukrainian].
5. Pivtorak KV. The role of systemic inflammation and endothelial dysfunction in pathogenesis of cardiovascular disease in patients with nonalcoholic fatty liver disease. J. Hepatol. 2016 Dec;64(2):S486. DOI: https://doi.org/10.1016/S0168-8278(16)00830-8
6. Finelli С, Tarantino G. What is the role of adiponectin in obesity related non-alcoholic fatty liver disease? World J Gastroenterol. 2013 Feb 14;19(6):802-12. PMCID: PMC3574877 DOI: 10,3748 / wjg.v19.i6.802
7. Polyzos SA, Toulis KA, Goulis DG, Zavos C, Kountouras J. Serum total adiponectin in nonalcoholic fatty liver disease: A systematic review and meta-analysis. Metabolism 2011 Mar; 60(3):313-26. PMID: 21040935 DOI: 10,1016 / j.metabol.2010.09.003
8. Kobyliak NM, Mykhalchyshyn HP, Savcheniuk OA, Falalieieva TM. Patofiziolohichna rol adyponektynu v rozvytku ozhyrinnia ta suputnikh zakhvoriuvan. Svit medytsyny ta biolohii. 2013;3(40):81-7. [in Ukrainian].
9. Brakenhielm E, Veitonmaki N, Cao R. Kihara Sh, Matsuzawa Yu, Zhivotovsky B, Funahashi T, et al. Adiponectininduced antiangiogenesis and antitumor activity involve caspasemediated endothelial cell apoptosis. Proc. Natl. Acad. Sci. USA. 2004 Feb 24;101(8):2476-81. PMCID: PMC356975
10. Koval VIu. Adypotsytokiny ta endotelialna dysfunktsiia pry khronichnomu pankreatyti. Ukraina. Zdorovia natsii. 2015;1(33):144-8. [in Ukrainian].
11. Federico A, Dallio M, Masarone M, Persico M, Loguercio C. The epidemiology of non-alcoholic fatty liver disease and its connection with cardiovascular disease: role of endothelial dysfunction. Eur Rev Med Pharmacol Sci. 2016 Nov;20(22):4731-41. PMID: 27906428.
12. Tsyntar TP, Fediv OI, Stupnytska HIa, Hluhovska SV. Endotelialna dysfunktsiia ta morfofunktsionalni vlastyvosti erytrotsytiv pry nealkoholnomu steatohepatyti, poiednanomu z khronichnym obstruktyvnym zakhvoriuvanniam lehen, u khvorykh na ozhyrinnia. Mizhnarodnyi endokrynolohichnyi zhurnal. 2017;13(6)415-9. DOI: http://dx.doi.org/10.22141/2224-0721.13.6.2017.112881 [in Ukrainian].
13. Skrypnyk IM, Maslova HS, Shcherbak OV. Osoblyvosti porushen stanu oksydu azotu u khvorykh na ishemichnu khvorobu sertsia v poiednanni z nealkoholnym steatohepatytom u dynamitsi patohenetychnoho likuvannia. Ukrainskyi terapevtychnyi zhurnal. 2017;(3):20-5. [in Ukrainian].
14. Svintsitskyi AS, Dzeman MI, Dynnyk NV. Osoblyvosti stanu zahalnoadaptyvnykh reaktsii orhanizmu pry zakhvoriuvanniakh pechinky. Suchasna hastroenterolohiia. 2012;4(66):47-52. [in Ukrainian].
15. Marsche G, Zelzer S, Meinitze A, Kern S, Meissl S, Pregartne G, et al. Adiponectin Predicts High-Density Lipoprotein Cholesterol Efflux Capacity in Adults Irrespective of Body Mass Index and Fat Distribution. J Clin Endocrinol Metab. 2017 Nov 1;102(11):4117-23. DOI: 10.1210/jc.201700933
16. Stanislavchuk MA, Al Salim AA, Zaichko NV. Zviazok dysadypokinemii z kardiometabolichnymy chynnykamy ta strukturno-funktsionalnym stanom sertsia u cholovikiv z pisliainfarktnym kardiosklerozom. Bukovynskyi medychnyi visnyk. 2017;21(1):154-9. [in Ukrainian].
17. Hontsariuk DO, Khrystych TM, Fediv OI, Teleki YaM. Rol S-reaktyvnoho bilka v rozvytku khronichnoi zapalnoi reaktsii, aterosklerozu, insulinorezystentnosti u khvorykh iz poiednanniam aterosklerozu ta khronichnoho pankreatytu. Praktychna anhiolohiia. 2012;3-4(52-53):21-5. [in Ukrainian].
18. Tereshchenko SN, Zhyrov YV, Malychenko EV, Kazantseva EЭ. Sravnytelnaia kharakterystyka ynhybytorov anhyotenzyn prevrashchaiushcheho fermenta ramypryla y эnalapryla v lechenyy khronycheskoi serdechnoi nedostatochnosty u zhenshchyn. Kardyolohyia. 2010;(4):64-8. [in Russiаn].

«Bulletin of problems biology and medicine» Issue 3 (145), 2018 year, 153-157 pages, index UDK 616.36-003.826-092:616.175.8

10.29254/2077-4214-2018-3-1-145-153-157