Chronic effects of aerobic exercise on gene expression of LOX-1 receptor in the heart of rats fed with high fat diet

Document Type: Original Article


1 Exercise Physiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

2 Department of Physiology and Biophysics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

3 Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran


Objective(s):Lectin-like low density lipoprotein receptor (LOX-1) has pivot role in vascular complications, which is upregulated in numerous pathological conditions. Since exercise has beneficial effects in prevention of hyperlipidemic complications, present study examined protective effects of aerobic exercise through reduction of LOX-1 expression in heart during dyslipidemia.
Materials and Methods: Four groups of rats were used (N=25): Normal, Normal and exercise, High fat and High fat and exercise. High fat diet (HFD) was made by adding 10% animal oil, 2% cholesterol and 0.5% colic acid to standard rodent chow. Exercise protocol consisted of swimming 1 hr/day, and 5 days/week for 8 weeks. Plasma lipids were evaluated at the end of experiment, 48 hr after final session of exercise. At the end, rats were sacrificed and heart was removed for determination of malondialdehyde (MDA) content, and LOX-1 expression.
Results:HFD meaningfully changed lipid profile (>50%), but chronic exercise had no significant effects on lipid profile. LOX-1 expression was significantly increased in heart of rats fed with HFD, while swimming exercise considerably reduced gene expression of LOX-1. MDA content was significantly enhanced in rats fed with HFD (4.37±0.6 nmol/mg, P<0.01) compared to normal group (1.56±0.48 nmol/mg), whereas swimming exercise decreased MDA level of heart in rats fed with HFD (2.28±0.32, P<0.01).
Conclusion:Findings indicated that swimming exercise is able to diminish heart expression of LOX-1 receptor concomitant reduction of oxidative stress. Since these parameters are involved in generation of dyslipidemic complications, swimming exercise is a good candidate to reduce these complications.


1. Kelley GA, Kelley KS. Efficacy of aerobic exercise on coronary heart disease risk factors. Prev Cardiol 2008; 11:71-75.

2. Tuzcu EM, Kapadia SR, Tutar E, Ziada KM, Hobbs RE, McCarthy PM, et al. High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults evidence from intravascular ultrasound. Circulation 2001; 103:2705-2710.

3.   Lahoz C, Mostaza J, Tranche S, Martin-Jadraque R, Mantilla M, López-Rodriguez I, et al. Atherogenic dyslipidemia in patients with established coronary artery disease. Nutr Metab Cardiovasc Dis 2012; 22:103-108.

4.   Rubenfire M, Brook RD, Rosenson RS. Treating mixed hyperlipidemia and the atherogenic lipid phenotype for prevention of cardiovascular events. Am J Med 2010; 123:892-898.

5.   Nejat A, Mirbolouk M, Mohebi R, Hasheminia M, Tohidi M, Saadat N, et al. Changes in lipid measures and incident coronary heart disease: Tehran Lipid & Glucose Study. Clin Biochem 2014; 47:1239-1244.

6.   Rizzo M, Kotur-Stevuljevic J, Berneis K, Spinas G, Rini GB, Jelic-Ivanovic Z, et al. Atherogenic dyslipidemia and oxidative stress: a new look. Transl Res 2009; 153:217-223.

7.   Jakus V. The role of free radicals, oxidative stress and antioxidant systems in diabetic vascular disease. Bratisl Lek Listy 2000; 101:541–551.

8.   Yan M, Mehta JL, Zhang W, Hu C. LOX-1, oxidative stress and inflammation: a novel mechanism for diabetic cardiovascular complications. Cardiovasc Drugs Ther 2011; 25:451-459.

9.   Adameova A, Xu Y, Duhamel T, Tappia P, Shan L, Dhalla N. Anti-atherosclerotic molecules targeting oxidative stress and inflammation. Curr Pharm Des 2009; 15:3094-3107.

10. Dominguez JH, Mehta JL, Li D, Wu P, Kelly KJ, Packer CS, et al. Anti-LOX-1 therapy in rats with diabetes and dyslipidemia: ablation of renal vascular and epithelial manifestations. Am J Physiol Renal Physiol 2008; 294:F110-9.

11. Akhmedov A, Rozenberg I, Paneni F, Camici GG, Shi Y, Doerries C, et al. Endothelial overexpression of LOX-1 increases plaque formation and promotes atherosclerosis in vivo. Eur Heart J 2014; 35:2839-2848.

12. Trejo-Gutierrez JF, Fletcher G. Impact of exercise on blood lipids and lipoproteins. J Clin Lipidol 2007; 1:175-181.

13. Joseph B. Physical activity in prevention and treatment of coronary disease: the battle line is in exercise vascular cell biology. Med Sci Sports Exerc 2004; 36:352-62.

14. Brochu M, Poehlman ET, Savage P, Fragnoli-Munn K, Ross S, Ades PA. Modest effects of exercise training alone on coronary risk factors and body composition in coronary patients. J Cardiopulm Rehabil 2000; 20:180-188.

15. Kannan U, Vasudevan K, Balasubramaniam K, Yerrabelli D, Shanmugavel K, John NA. Effect of Exercise Intensity on Lipid Profile in Sedentary Obese Adults. Journal of J Clin Diagn Res 2014; 8:8-10.

16. Koivula RW, Tornberg AB, Franks PW. Exercise and diabetes-related cardiovascular disease: systematic review of published evidence from observational studies and clinical trials. Curr Diab Rep 2013; 13:372-380.

17. Blair SN, Kampert JB, Kohl HW, Barlow CE, Macera CA, Paffenbarger RS, et al. Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA 1996; 276:205-210.

18. Iemitsu M, Fujie S, Murakami H, Sanada K, Kawano H, Gando Y, et al. Higher cardiorespiratory fitness attenuates the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism. Eur J Appl Physiol 2014: 114:1-8.

19. Ramachandran S, Penumetcha M, Merchant NK, Santanam N, Rong R, Parthasarathy S. Exercise reduces preexisting atherosclerotic lesions in LDL receptor knock out mice. Atherosclerosis 2005; 178:33-38.

20. Shimada K, Kishimoto C, Okabe TA, Hattori M, Murayama T, Yokode M, et al. Exercise training reduces severity of atherosclerosis in apolipoprotein E knockout mice via nitric oxide. Circ J 2007; 71:1147-1151.

21. Okabe TA, Shimada K, Hattori M, Murayama T, Yokode M, Kita T, et al. Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects. Cardiovasc Res 2007; 74:537-545.

22. Mann S, Beedie C, Jimenez A. Differential effects on cholesterol and lipid profile of physical activity, aerobic exercise, resistance training and combined exercise modalities: A review and synthesis. Sports Med 2014; 44:211-221.

23. Heidarian E, Jafari-Dehkordi E, Seidkhani-Nahal A. Effect of garlic on liver phosphatidate phosphohydrolase and plasma lipid levels in hyperlipidemic rats. Food Chem Toxicol 2011; 49:1110-1114.

24. Thomas TR, Pellechia J, Rector RS, Sun GY, Sturek MS, Laughlin MH. Exercise training does not reduce hyperlipidemia in pigs fed a high-fat diet. Metabolism 2002; 51:1587-1595.

25. Teerapornpuntakit J, Dorkkam N, Wongdee K, Krishnamra N, Charoenphandhu N. Endurance swimming stimulates transepithelial calcium transport and alters the expression of genes related to calcium absorption in the intestine of rats. Am J Physiol Endocrinol Metab 2009; 296:775-786.

26. Ishino S, Mukai T, Kume N, Asano D, Ogawa M, Kuge Y, et al. Lectin-like oxidized LDL receptor-1 (LOX-1) expression is associated with atherosclerotic plaque instability--analysis in hypercholesterolemic rabbits. Atherosclerosis 2007; 195:48-56.

27. Kataoka H, Kume N, Miyamoto S, Minami M, Moriwaki H, Murase T, et al. Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions. Circulation 1999; 99:3110-3117.

28. Chen H, Li D, Sawamura T, Inoue K, Mehta JL. Upregulation of LOX-1 expression in aorta of hypercholesterolemic rabbits: modulation by losartan. Biochem Biophys Res Commun 2000; 276:1100-1104.

29. Nagase M, Ando K, Nagase T, Kaname S, Sawamura T, Fujita T. Redox-Sensitive Regulation of LOX-1 Gene Expression in Vascular Endothelium. Biochem Biophys Res Commun 2001; 281:720–725.

30. Mehta JL, Chen J, Hermonat PL, Romeo F, Novelli G. Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders. Cardiovasc Res 2006; 69:36-45.

31. Szostak J, Laurant P. The forgotten face of regular physical exercise: a natural anti-atherogenic activity. Clin Sci 2011; 121:91-106.

32. Hardman AE. Interaction of physical activity and diet: implications for lipoprotein metabolism. Public Health Nutr 1999; 2:369-376.

33. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med 2002; 347:1483-1492.

34. Karabulut AB, Kafkas ME, Kafkas AS, Onal Y, Kiran TR. The effect of regular exercise and massage on oxidant and antioxidant parameters. Indian J Physiol Pharmacol 2013; 57:378-383.

35. Wang JS, Chow SE, Chen JK, Wong MK. Effect of exercise training on oxidized LDL-mediated platelet function in rats. Thromb Haemost 2000;83:503-508.

36. Niebauer J, Maxwell AJ, Lin PS, Tsao PS, Kosek J, Bernstein D, et al. Impaired aerobic capacity in hypercholesterolemic mice: partial reversal by exercise training. Am J Physiol 1999; 276:1346-1354.

37. Kojda G, Harrison D. Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. Cardiovasc Res 1999; 43:652-671.

38. Raij L. Nitric oxide in the pathogenesis of cardiac disease. J Clin Hypertens 2006; 8:30-39.

39. Thompson MA, Henderson KK, Woodman CR, Turk JR, Rush JW, Price E, et al. Exercise preserves endothelium-dependent relaxation in coronary arteries of hypercholesterolemic male pigs. J Appl Physiol 2004; 96:1114-1126.