1Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran
2Department of Anatomy, Isfahan University of Medical Sciences, Isfahan, Iran
Objective(s): Atherosclerosis is a chronic immune-inflammatory disease that generally leads to ischemic heart disease. Ghrelin has several modulatory effects on cardiovascular system. In this study, we investigated the effect of ghrelin on aortic intima-media thickness, size and the number of adipocyte cells in obese and control mice. Materials and Methods:This study was conducted on 24 male C57BL/6 mice. The animals were divided into four groups: control, obese (received high fat diet), control+ghrelin (injected with 100 µg/Kg subcutaneously, bid) and obese+ghrelin (n=6 each). After 10 days, animals were sacrificed and epididymal adipose tissue and thoracic aortae were removed. Adipocyte cell number, size and aortic intima-media thickness were evaluated. Results:Ghrelin did not change adipocyte cell number and size and aortic intima-media thickness in obese and control mice. In this study, high fat diet significantly decreased the number of adipocyte cells while increased their size (P<0.05). Ghrelin administration had no significant effect on adipocyte cell number and size in obese and control groups (P >0.05). In addition, it could not alter aortic intima-media thickness in both groups. Conclusion: Although ghrelin has several cardiovascular effects, it seems that it could not alter the size and number of adipocyte cells and aortic intima-media thickness in diet-induced obese mice
1. Bobryshev YV. Monocyte recruitment and foam cell formation in atherosclerosis. Micron 2006; 37:208-222.
2. Ozbay Y, Aydin S, Dagli AF, Akbulut M, Dagli N, Kilic N, et- al. Obestatin is present in saliva: alterations in obestatin and ghrelin levels of saliva and serum in ischemic heart disease. BMB Rep 2008; 41:55-61.
3. Farmer JA, Torre-Amione G. Atherosclerosis and inflammation. Curr Atheroscler Rep 2002; 4:92-98.
4. Stocker R, Keaney JF. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004; 84:1381-41478.
5. Shamseddeen H, Getty JZ, Hamdallah IN, Ali MR. Epidemiology and economic impact of obesity and type 2 diabetes. Surg Clin North Am 2011; 91:1163-1172.
6. Wu ZH, Zhao SP. Adipocyte: a potential target for the treatment of atherosclerosis. Med Hypotheses 2006; 67:82-86.
7. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond) 2008; 32:1431-1437.
8. Ferroni P, Basili S, Falco A, Davi G. Inflammation, insulin resistance, and obesity. Curr Atheroscler Rep 2004; 6:424-431.
9. Zhao SP, Wu J, Zhang DQ, Ye HJ, Liu L, Li JQ. Fenofibrate enhances CD36 mediated endocytic uptake and degradation of oxidized low density lipoprotein in adipocytes from hypercholesterolemia rabbit. Atherosclerosis 2004; 177:255-262.
10. Tesauro M, Schinzari F, Caramanti M, Lauro R, Cardillo C. Metabolic and cardiovascular effects of ghrelin. Int J Pept 2010;2010.
11. KojimaM, Kangawa K. Ghrelin: structure and function. Physiol Rev 2005; 85:495-522.
12. Leite-Moreira AF, Soares JB. Physiological, pathological and potential therapeutic roles of ghrelin. Drug Discov Today 2007; 12:276-288.
13. Zhang M, FangWY, Yuan F, Qu XK, Liu H, Xu YJ, et al. Plasma ghrelin levels are closely associated with severity and morphology of angiographically-detected coronary atherosclerosis in Chineses patients with diabetes mellitus. Acta Pharmacol Sin 2012; 33:452-458.14. Kellokoski E, Kunnari A, Jokela M, Makela S, Kesaniemi YA, Horkko S. Ghrelin and obestatin modulate early atherogenic processes on cells: enhancement of monocyte adhesion and oxidized low-density lipoprotein binding. Metabolism 2009; 58:1572-1580.
15. Habegger KM, Grant E, Pfluger PT, Perez-Tilve D, Daugherty A, Bruemmer D, et al. Ghrelin Receptor Deficiency does not Affect Diet-Induced Atherosclerosis in Low-Density Lipoprotein Receptor-Null Mice. Front Endocrinol (Lausanne) 2011; 2:67.
16. Peyot ML, Pepin E, Lamontagne J, Latour MG, Zarrouki B, Lussier R, et al. Beta-cell failure in diet-induced obese mice stratified according to body weight gain: secretory dysfunction and altered islet lipid metabolism without steatosis or reducedbeta-cell mass. Diabetes 2010; 59:2178-2187.
17. Li L, Zhang LK, Pang YZ, Pan CS, Qi YF, Chen L, et al. Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats. Acta Pharmacol Sin 2006; 27:527-535.
18. Dileepan KN, Johnston TP, Li Y, Tawfik O, Stechschulte DJ. Deranged aortic intima-media thickness, plasma triglycerides and granulopoiesis in Sl/Sl(d) mice. Mediators Inflamm 2004; 13:335-341.
19. Miegueu P, St PD, Broglio F, Cianflone K. Effect of desacyl ghrelin, obestatin and related peptides on triglyceride storage, metabolism and GHSR signaling in 3T3-L1 adipocytes. J Cell Biochem 2011; 112:704-714.
20. O'Connell J, Lynch L, Cawood TJ, Kwasnik A, Nolan N, Geoghegan J, et al. The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity. PLoS One 2010; 5:e9997.
21. Raz I, Eldor R, Cernea S, Shafrir E. Diabetes: insulin resistance and derangements in lipid metabolism. Curethrough intervention in fat transport and storage. Diabetes Metab Res Rev 2005; 21:3-14.
22. Leibson CL, Williamson DF, Melton LJ, III, Palumbo PJ, Smith SA, Ransom JE, et al. Temporal trends in BMI among adults with diabetes. Diabetes Care 2001; 24:1584-1589.
23. Chang L, Ren Y, Liu X, Li WG, Yang J, Geng B, et al. Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart. J Cardiovasc Pharmacol 2004; 43:165-170.
24. Granata R, Isgaard J, Alloatti G, Ghigo E. Cardiovascular actions of the ghrelin gene-derived peptides and growth hormone-releasing hormone. Exp Biol Med (Maywood ) 2011; 236:505-514.
25. Davies JS, Kotokorpi P, Eccles SR, Barnes SK, Tokarczuk PF, Allen SK, et al. Ghrelin inducesabdominal obesity via GHS-R-dependent lipid retention. Mol Endocrinol 2009; 23:914-924.
26. Lin L, Saha PK, Ma X, Henshaw IO, Shao L, Chang BH, et- al. Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues. Aging Cell 2011; 10:996-1010.
27. Kadoglou NP, Sailer N, Moumtzouoglou A, Kapelouzou A, Tsanikidis H, Vitta I, et al. Visfatin (nampt) and ghrelin as novel markers of carotid atherosclerosis in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 2010; 118:75-80.
28. Suematsu M, Katsuki A, Sumida Y, Gabazza EC, Murashima S, Matsumoto K, et al. Decreased circulating levels of active ghrelin are associated with increasedoxidative stress in obese subjects. Eur J Endocrinol 2005; 153:403-407.
29. Skilton MR, Nakhla S, Sieveking DP, Caterson ID, Celermajer DS. Pathophysiological levels of the obesity related peptides resistin and ghrelin increase adhesion molecule expression on human vascular endothelial cells. Clin Exp Pharmacol Physiol 2005; 32:839-844.
30. Genis BB, Granada ML, Alonso N, Lauzurica R, Jimenez JA, Barluenga E, et al. Ghrelin, glucose homeostasis, and carotid intima media thickness in kidney transplantation. Transplantation 2007; 84:1248-1254.