High-fat diet induced cardiac hemodynamic changes: effects of exercise and obestatin

Year 2023, Volume: 27 Issue: 1, 404 - 413, 28.06.2025

Gülsün Memi , Levent Öztürk , Orkide Palabıyık

Abstract

The obese population has been rapidly increasing because of high-fat consumption and a sedentary lifestyle. Large amounts of dietary fat intake increase the risk of cardiovascular disease. We aimed to investigate the effects of exercise and obestatin on a high-fat diet (HFD) induced cardiac hemodynamic changes. Seventy-nine Sprague Dawley rats (200 to 250 g) were fed either control diet or HFD for 8 weeks. In the 5th week, each diet group was subgrouped as follows; control, exercise, obestatin (25μg/kg, i.p), exercise+obestatin (25μg/kg, i.p). After the end of 4 weeks of exercise (swimming exercise, 5 days a week/ 20 min day) and obestatin administration period, all animals were sacrificed. Hearts were removed for hemodynamic measurements with the Langendorff apparatus. Blood samples were collected for biochemical measurements. Data were analyzed by Graphpad Prism 6.0. and p<0.05 was accepted as statistically significant. Cardiac contractility and hemodynamic parameters in the HFD model have been evaluated. And the effects of chronic obestatin treatment and exercise were studied together. Obestatin ameliorated derangements in LVDP, heart rate, and blood lipid levels induced by an HFD. Also, obestatin prevents decreasing BNP levels with high fat consumption. Obestatin treatment potentiated the beneficial effects of exercise evidenced by LVDP, heart rate, blood lipids, BNP, and AT2R1 measurements. We believe that obestatin has the potential for the maintenance of cardiac function in HFD.

Keywords

Obesity , high-fat diet , Langendorff , obestatin , exercise , HDL

References

• [1] Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 2019. 393(10184): p. 1958-1972. [CrossRef]
• [2] Engin A. Eat and Death: Chronic Over-Eating. Adv Exp Med Biol, 2017. 960: p. 53-80. [CrossRef]
• [3] Che Y, Wang ZP, Yuan Y, Zhang N, Jin YG, Wan CX, Tang QZ. Role of autophagy in a model of obesity: A long‑term high fat diet induces cardiac dysfunction. Mol Med Rep, 2018. 18(3): p. 3251-3261 [CrossRef]
• [4] Lizardo K, Ayyappan JP, Cui MH, Balasubramanya R, Jelicks LA, Nagajyothi JF. High fat diet aggravates cardiomyopathy in murine chronic Chagas disease. Microbes Infect, 2019. 21(1): p. 63-71. [CrossRef]
• [5] Zhang F, Hartnett S, Sample A, Schnack S, Li Y. High fat diet induced alterations of atrial electrical activities in mice. Am J Cardiovasc Dis, 2016. 6(1): p. 1-9.
• [6] Littlejohns B, Lin H, Angelini GD, Halestrap AP, Suleiman MS. Switching back to normal diet following high-fat diet feeding reduces cardiac vulnerability to ischaemia and reperfusion injury. Cell Physiol Biochem, 2014. 34(4): p. 1090-100. [CrossRef]
• [7] Ren AJ, He Q, Shi JS, Guo ZF, Zheng X, Lin L, Wang YK, Xia SY, Sun LL, Du X, Sun Y, Zhang LM, Yuan WJ. Association of obestatin with blood pressure in the third trimesters of pregnancy. Peptides, 2009. 30(9): p. 1742-5. [CrossRef]
• [8] Su XJ, Dong RX, Li YP, Yang SG, Li ZF. Obestatin and cardiovascular health. Peptides, 2014. 52: p. 58-60. [CrossRef]
• [9] Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJ. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science, 2005. 310(5750): p. 996-9. [CrossRef]
• [10] Aragno M, Mastrocola R, Ghé C, Arnoletti E, Bassino E, Alloatti G, Muccioli G. Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms. Cardiovasc Diabetol, 2012. 11: p. 129. [CrossRef]
• [11] Li HQ, Wu YB, Yin CS, Chen L, Zhang Q, Hu LQ. Obestatin attenuated doxorubicin-induced cardiomyopathy via enhancing long noncoding Mhrt RNA expression. Biomed Pharmacother, 2016. 81: p. 474-481. [CrossRef]
• [12] Li ZF, Guo ZF, Cao J, Hu JQ, Zhao XX, Xu RL, Huang XM, Qin YW, Zheng X. Plasma ghrelin and obestatin levels are increased in spontaneously hypertensive rats. Peptides, 2010. 31(2): p. 297-300. [CrossRef]
• [13] Ren AJ, Guo ZF, Wang YK, Lin L, Zheng X, Yuan WJ. Obestatin, obesity and diabetes. Peptides, 2009. 30(2): p. 439-44. [CrossRef]
• [14] Sazdova I, Ilieva BM, Minkov IB, Schubert R, Gagov HS. Obestatin as contractile mediator of excised frog heart. Central European Journal of Biology, 2009. 4: p. 327-334. [CrossRef]
• [15] Chung E, Grue KA, Kaur G, Mallory B, Serrano CR, Ullevig SL, Kottapalli KR, Lee SC, Dufour JM, Shen CL, Umeda M. Maternal exercise before and during pregnancy alleviates metabolic dysfunction associated with high-fat diet in pregnant mice, without significant changes in gut microbiota. Nutr Res, 2019. 69: p. 42-57. [CrossRef]
• [16] Ghanbari-Niaki A, Jafari A, Abednazari H, Nikbakht H. Treadmill exercise reduces obestatin concentrations in rat fundus and small intestine. Biochem Biophys Res Commun, 2008. 372(4): p. 741-5. [CrossRef]
• [17] Tokudome T, Kishimoto I, Miyazato M, Kangawa K. Ghrelin and the cardiovascular system. Front Horm Res, 2014. 43: p. 125-33. [CrossRef]
• [18] Acikel Elmas M, Cakici SE, Dur IR, Kozluca I, Arınc M, Binbuga B. Bingol Ozakpınar O, Kolgazi M, Sener G, Ercan F. Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats. Tissue Cell, 2019. 57: p. 57-65. [CrossRef]
• [19] Fang J, Tang M. Exercise improves high fat diet-impaired vascular function. Biomed Rep, 2017. 7(4): p. 337-342. [CrossRef]
• [20] Li W, Chang M, Qiu M, Chen Y, Zhang X, Li Q, Cui C. Exogenous obestatin decreases beta-cell apoptosis and alfa-cell proliferation in high fat diet and streptozotocin induced type 2 diabetic rats. Eur J Pharmacol, 2019. 851: p. 36-42. [CrossRef]
• [21] Cowan E, Burch KJ, Green BD, Grieve DJ. Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes. Br J Pharmacol, 2016. 173(14): p. 2165-81. [CrossRef]
• [22] Chen D, Li X, Zhang L, Zhu M, Gao L. A high-fat diet impairs mitochondrial biogenesis, mitochondrial dynamics, and the respiratory chain complex in rat myocardial tissues. J Cell Biochem, 2018. 119(11): p. 9602. [CrossRef]
• [23] Yoon GE, Jung JK, Lee YH, Jang BC, In Kim J. Histone deacetylase inhibitor CG200745 ameliorates high-fat diet-induced hypertension via inhibition of angiotensin II production. Naunyn Schmiedebergs Arch Pharmacol, 2020. 393(3): p. 491-500. [CrossRef]
• [24] Bruder-Nascimento T, Ekeledo OJ, Anderson R, Le HB, de Chantemèle EJB. Long Term High Fat Diet Treatment: An Appropriate Approach to Study the Sex-Specificity of the Autonomic and Cardiovascular Responses to Obesity in Mice. Front Physiol, 2017. 8: p. 32. [CrossRef]
• [25] Siddeek B, Mauduit C, Chehade H, Blin G, Liand M, Chindamo M, Benahmed M, Simeoni U. Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis. Cell Death Discov, 2019. 5: p. 71. [CrossRef]
• [26] Li ZF, Song SW, Qin YW, Zhang JL, Zhao XX, Zhang BL, Ren AJ, Guo ZF, Zheng X. Bolus intravenous injection of obestatin does not change blood pressure level of spontaneously hypertensive rat. Peptides, 2009. 30(10): p. 1928-30. [CrossRef]
• [27] Prokic V, Plecevic S, Bradic J, Petkovic A, Srejovic I, Bolevich S, Jeremic J, Bolevich S, Jakovljevic V, Zivkovic V. The impact of nine weeks swimming exercise on heart function in hypertensive and normotensive rats: role of cardiac oxidative stress. J Sports Med Phys Fitness, 2019. 59(12): p. 2075-2083. [CrossRef]
• [28] Plecevic S, Jakovljevic B, Savic M, Zivkovic V, Nikolic T, Jeremic J, Milosavljevic I, Srejovic I, Tasic N, Djuric D, Jakovljevic V. Comparison of short-term and medium-term swimming training on cardiodynamics and coronary flow in high salt-induced hypertensive and normotensive rats. Mol Cell Biochem, 2018. 447(1-2): p. 33-45. [CrossRef]
• [29] Penna C, Tullio F, Femminò S, Rocca C, Angelone T, Cerra MC, Gallo MP, Gesmundo I, Fanciulli A, Brizzi MF, Pagliaro P, Alloatti G, Granata R. Obestatin regulates cardiovascular function and promotes cardioprotection through the nitric oxide pathway. J Cell Mol Med, 2017. 21(12): p. 3670-3678. [CrossRef]
• [30] Otvos JD, Mora S, Shalaurova I, Greenland P, Mackey RH, Goff DC Jr. Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. J Clin Lipidol, 2011. 5(2): p. 105-13. [CrossRef]
• [31] Fan Q, Yin X, Rababa'h A, Diaz Diaz A, Wijaya CS, Singh S, Suryavanshi SV, Vo HH, Saeed M, Zhang Y, McConnell BK. Absence of gravin-mediated signaling inhibits development of high-fat diet-induced hyperlipidemia and atherosclerosis. Am J Physiol Heart Circ Physiol, 2019. 317(4): p. H793-h810. [CrossRef]
• [32] Zhao X, Zhu J, Wang L, Li Y, Zhao T, Chen X, Sun Y, Dai Y, Wei G, Altamirano A, Zhang T, Yan Z. U. diffracta extract mitigates high fat diet and VD3-induced atherosclerosis and biochemical changes in the serum liver and aorta of rats. Biomed Pharmacother, 2019. 120: p. 109446. [CrossRef]
• [33] Tiyerili V, Becher UM, Camara B, Yildirimtürk C, Aksoy A, Kebschull M, Werner N, Nickenig G, Müller C. Impact of peroxisome proliferator-activated receptor γ on angiotensin II type 1 receptor-mediated insulin sensitivity, vascular inflammation and atherogenesis in hypercholesterolemic mice. Arch Med Sci, 2015. 11(4): p. 877-85. [CrossRef]
• [34] Leger T, Hininger-Favier I, Capel F, Geloen A, Rigaudière JP, Jouve C, Pitois E, Pineau G, Vaysse C, Chardigny JM, Michalski MC, Malpuech-Brugère C, Demaison L. Dietary canolol protects the heart against the deleterious effects induced by the association of rapeseed oil, vitamin E and coenzyme Q10 in the context of a high-fat diet. Nutr Metab (Lond), 2018. 15: p. 15. [CrossRef]
• [35] Li KY, Zhang YJ. Valsartan-induced cardioprotection involves angiotensin II type 2 receptor upregulation in isolated ischaemia and reperfused rat hearts. Acta Cardiol, 2015. 70(1): p. 67-72. [CrossRef]
• [36] Maalouf R, Bailey S. A review on B-type natriuretic peptide monitoring: assays and biosensors. Heart Fail Rev, 2016. 21(5): p. 567-78. [CrossRef]
• [37] Novi D, Vidigal CB, Marques BVD, Forcato S, Raquel HA, Zaia DAM, Zaia C, Martins-Pinge MC, Gerardin DCC, Ceravolo GS. Can maternal treatment with metformin during gestation and lactation cause metabolic and cardiovascular disorders in rat offspring? Arch Physiol Biochem, 2020. 126(3): p. 276-281. [CrossRef]
• [38] Yuce B, Danis O, Ogan A, Sener G, Bulut M, Yarat A. Antioxidative and lipid lowering effects of 7,8-dihydroxy-3- (4-methylphenyl) coumarin in hyperlipidemic rats. Arzneimittelforschung, 2009. 59(3): p. 129-34. [CrossRef]
• [39] Rocha LA, Petriz BA, Borges DH, Oliveira RJ, de Andrade RV, Domont GB, Pereira RW, Franco OL. High molecular mass proteomics analyses of left ventricle from rats subjected to differential swimming training. BMC Physiol, 2012. 12: p. 11. [CrossRef]
• [40] Vardar SA, Palabiyik O, Topuz RD, Gürel EE, Caliskan S, Topçu Özen S, Süt N, Karadağ ÇH. Hemodynamic effects of atrial natriuretic peptide in ischemia-repertusion injury that occurs after exercise. Turk J Med Sci, 2015. 45(2): p. 298-305. [CrossRef]