Nutr Res Pract.  2012 Dec;6(6):513-519.

Aged garlic extract enhances exercise-mediated improvement of metabolic parameters in high fat diet-induced obese rats

• Seo DY
• Lee S
• Figueroa A
• Kwak YS
• Kim N
• Rhee BD
• Ko KS
• Bang HS
• Baek YH
• Han J

Abstract

Aged garlic extract (AGE) is known to have a protective effect against immune system, endothelial function, oxidative stress and inflammation. We examined the effects of exercise with and without aged garlic extract administration on body weight, lipid profiles, inflammatory cytokines, and oxidative stress marker in high-fat diet (HFD)-induced obese rats. Forty-five Sprague-Dawley rats were fed either a HFD (HFD, n = 40) or a normal diet (ND, n = 5) for 6 weeks and thereafter randomized into ND (n = 5), HFD (n = 10), HFD with AGE (n = 10), HFD with Exercise (n = 10), or HFD with Exercise+AGE (n = 10) for 4 weeks. AGE groups were administered at a dose of 2.86 g/kg.body weight, orally. Exercise consisted of running 15-60 min 5 days/week with gradually increasing intensity. AGE (P < 0.01), Exercise, and Exercise+AGE (P < 0.001) attenuated body weight gain and food efficiency ratio compared to HFD. Visceral fat and liver weight gain were attenuated (P < 0.05) with all three interventions with a greater effect on visceral fat in the Exercise+AGE than AGE (P < 0.001). In reducing visceral fat (P < 0.001), epididymal fat (P < 0.01) and liver weight (P < 0.001), Exercise+AGE was effective, but exercise showed a stronger suppressive effect than AGE. Exercise+AGE showed further additive effects on reducing visceral fat and liver weight (P < 0.001). AGE significantly attenuated the increase in total cholesterol and low-density lipoprotein-cholesterol compared with HFD (P < 0.05). Exercise+AGE attenuated the increase in triglycerides compared with HFD (P < 0.05). Exercise group significantly decrease in C-reactive protein (P < 0.001). These results suggest that AGE supplementation and exercise alone have anti-obesity, cholesterol lowering, and anti-inflammatory effects, but the combined intervention is more effective in reducing weight gain and triglycerides levels than either intervention alone.

Keyword

Aged garlic extract; exercise; high fat diet; obesity; metabolic parameters

MeSH Terms

Aged
Animals
Body Weight
C-Reactive Protein
Cholesterol
Cytokines
Diet
Diet, High-Fat
Garlic
Humans
Immune System
Inflammation
Intra-Abdominal Fat
Liver
Obesity
Oxidative Stress
Rats
Rats, Sprague-Dawley
Running
Triglycerides
Weight Gain
C-Reactive Protein
Cholesterol
Cytokines
Triglycerides

Figure

• 

  Fig. 1 Effect of AGE supplementation on body weight in HFD-induced obese rats with or without AGE supplementation for 4 weeks. AGE was orally administered at a dose of 2.86 g/kg 30 min before exercise. Statistical analysis was performed using one-way ANOVA. Values are means ± SD. **P < 0.01 and ***P < 0.001 vs. HFD.

Reference

1. Goran MI, Treuth MS. Energy expenditure, physical activity, and obesity in children. Pediatr Clin North Am. 2001. 48:931–953.

2. Kennedy RL, Chokkalingham K, Srinivasan R. Obesity in the elderly: who should we be treating, and why, and how? Curr Opin Clin Nutr Metab Care. 2004. 7:3–9.

3. Steinberger J, Daniels SR. American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young). American Heart Association Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Circulation. 2003. 107:1448–1453.

4. Yang G, Badeanlou L, Bielawski J, Roberts AJ, Hannun YA, Samad F. Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome. Am J Physiol Endocrinol Metab. 2009. 297:E211–E224.

5. Ansell BJ, Watson KE, Fogelman AM, Navab M, Fonarow GC. High-density lipoprotein function recent advances. J Am Coll Cardiol. 2005. 46:1792–1798.

6. Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001. 344:1343–1350.

7. Gollisch KS, Brandauer J, Jessen N, Toyoda T, Nayer A, Hirshman MF, Goodyear LJ. Effects of exercise training on subcutaneous and visceral adipose tissue in normal- and high-fat diet-fed rats. Am J Physiol Endocrinol Metab. 2009. 297:E495–E504.

8. Wang X, Cheng M, Zhao M, Ge A, Guo F, Zhang M, Yang Y, Liu L, Yang N. Differential effects of high-fat-diet rich in lard oil or soybean oil on osteopontin expression and inflammation of adipose tissue in diet-induced obese rats. Eur J Nutr. 2012. Forthcoming.

9. Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol. 2008. 8:923–934.

10. Szekanecz Z. Pro-inflammatory cytokines in atherosclerosis. Isr Med Assoc J. 2008. 10:529–530.

11. Quak SH, Furnes R, Lavine J, Baur LA. Obesity Working Group. Obesity in children and adolescents. J Pediatr Gastroenterol Nutr. 2008. 47:254–259.

12. Tzotzas T, Evangelou P, Kiortsis DN. Obesity, weight loss and conditional cardiovascular risk factors. Obes Rev. 2011. 12:e282–e289.

13. Li W, Wang D, Song G, Zuo C, Qiao X, Qin S. The effect of combination therapy of allicin and fenofibrate on high fat diet-induced vascular endothelium dysfunction and liver damage in rats. Lipids Health Dis. 2010. 9:131.

14. Karmakar S, Das D, Maiti A, Majumdar S, Mukherjee P, Das AS, Mitra C. Black tea prevents high fat diet-induced non-alcoholic steatohepatitis. Phytother Res. 2011. 25:1073–1081.

15. Cao ZH, Gu DH, Lin QY, Xu ZQ, Huang QC, Rao H, Liu EW, Jia JJ, Ge CR. Effect of pu-erh tea on body fat and lipid profiles in rats with diet-induced obesity. Phytother Res. 2011. 25:234–238.

16. Seo EY, Ha AW, Kim WK. Alpha-lipoic acid reduced weight gain and improved the lipid profile in rats fed with high fat diet. Nutr Res Pract. 2012. 6:195–200.

17. Banerjee SK, Maulik SK. Effect of garlic on cardiovascular disorders: a review. Nutr J. 2002. 1:4.

18. Amagase H, Petesch BL, Matsuura H, Kasuga S, Itakura Y. Intake of garlic and its bioactive components. J Nutr. 2001. 131:955S–962S.

19. Yeh YY, Yeh SM. Garlic reduces plasma lipids by inhibiting hepatic cholesterol and triacylglycerol synthesis. Lipids. 1994. 29:189–193.

20. Ide N, Lau BH. Aged garlic extract attenuates intracellular oxidative stress. Phytomedicine. 1999. 6:125–131.

21. Zare A, Farzaneh P, Pourpak Z, Zahedi F, Moin M, Shahabi S, Hassan ZM. Purified aged garlic extract modulates allergic airway inflammation in BALB/c mice. Iran J Allergy Asthma Immunol. 2008. 7:133–141.

22. Xu X, Ying Z, Cai M, Xu Z, Li Y, Jiang SY, Tzan K, Wang A, Parthasarathy S, He G, Rajagopalan S, Sun Q. Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2011. 300:R1115–R1125.

23. Touati S, Meziri F, Devaux S, Berthelot A, Touyz RM, Laurant P. Exercise reverses metabolic syndrome in high-fat diet-induced obese rats. Med Sci Sports Exerc. 2011. 43:398–407.

24. Torrens C, Hanson MA, Gluckman PD, Vickers MH. Maternal undernutrition leads to endothelial dysfunction in adult male rat offspring independent of postnatal diet. Br J Nutr. 2009. 101:27–33.

25. Moriguchi T, Saito H, Nishiyama N. Aged garlic extract prolongs longevity and improves spatial memory deficit in senescence-accelerated mouse. Biol Pharm Bull. 1996. 19:305–307.

26. Morihara N, Ushijima M, Kashimoto N, Sumioka I, Nishihama T, Hayama M, Takeda H. Aged garlic extract ameliorates physical fatigue. Biol Pharm Bull. 2006. 29:962–966.

27. Boor P, Celec P, Behuliak M, Grancic P, Kebis A, Kukan M, Pronayová N, Liptaj T, Ostendorf T, Sebeková K. Regular moderate exercise reduces advanced glycation and ameliorates early diabetic nephropathy in obese Zucker rats. Metabolism. 2009. 58:1669–1677.

28. Iyer A, Kauter K, Alam MA, Hwang SH, Morisseau C, Hammock BD, Brown L. Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats. Exp Diabetes Res. 2012. 2012:758614.

29. Handa P, Tateya S, Rizzo NO, Cheng AM, Morgan-Stevenson V, Han CY, Clowes AW, Daum G, O'Brien KD, Schwartz MW, Chait A, Kim F. Reduced vascular nitric oxide-cGMP signaling contributes to adipose tissue inflammation during high-fat feeding. Arterioscler Thromb Vasc Biol. 2011. 31:2827–2835.

30. Burneiko RC, Diniz YS, Galhardi CM, Rodrigues HG, Ebaid GM, Faine LA, Padovani CR, Cicogna AC, Novelli EL. Interaction of hypercaloric diet and physical exercise on lipid profile, oxidative stress and antioxidant defenses. Food Chem Toxicol. 2006. 44:1167–1172.

31. Buettner R, Parhofer KG, Woenckhaus M, Wrede CE, Kunz-Schughart LA, Schölmerich J, Bollheimer LC. Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J Mol Endocrinol. 2006. 36:485–501.

32. Jakicic JM. Exercise in the treatment of obesity. Endocrinol Metab Clin North Am. 2003. 32:967–980.

33. Hagan S, Niswender KD. Neuroendocrine regulation of food intake. Pediatr Blood Cancer. 2012. 58:149–153.

34. Flores MB, Fernandes MF, Ropelle ER, Faria MC, Ueno M, Velloso LA, Saad MJ, Carvalheira JB. Exercise improves insulin and leptin sensitivity in hypothalamus of Wistar rats. Diabetes. 2006. 55:2554–2561.

35. Maljaars J, Peters HP, Masclee AM. Review article: The gastrointestinal tract: neuroendocrine regulation of satiety and food intake. Aliment Pharmacol Ther. 2007. 26:Suppl 2. 241–250.

36. Mastorakos G, Zapanti E. The hypothalamic-pituitary-adrenal axis in the neuroendocrine regulation of food intake and obesity: the role of corticotropin releasing hormone. Nutr Neurosci. 2004. 7:271–280.

37. Kawaguchi H, Miyoshi N, Miura N, Fujiki M, Horiuchi M, Izumi Y, Miyajima H, Nagata R, Misumi K, Takeuchi T, Tanimoto A, Yoshida H. Microminipig, a non-rodent experimental animal optimized for life science research:novel atherosclerosis model induced by high fat and cholesterol diet. J Pharmacol Sci. 2011. 115:115–121.

38. Rector RS, Thyfault JP, Morris RT, Laye MJ, Borengasser SJ, Booth FW, Ibdah JA. Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty rats. Am J Physiol Gastrointest Liver Physiol. 2008. 294:G619–G626.

39. Gauthier MS, Couturier K, Latour JG, Lavoie JM. Concurrent exercise prevents high-fat-diet-induced macrovesicular hepatic steatosis. J Appl Physiol. 2003. 94:2127–2134.

40. Durak I, Kavutcu M, Aytaç B, Avci A, Devrim E, Ozbek H, Oztürk HS. Effects of garlic extract consumption on blood lipid and oxidant/antioxidant parameters in humans with high blood cholesterol. J Nutr Biochem. 2004. 15:373–377.

41. Estadella D, Oyama LM, Dâmaso AR, Ribeiro EB, Oller Do Nascimento CM. Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats. Nutrition. 2004. 20:218–224.

42. Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H. Effect of physical exercise on sensitivity and responsiveness to insulin in humans. Am J Physiol. 1988. 254:E248–E259.

43. Yeh YY, Liu L. Cholesterol-lowering effect of garlic extracts and organosulfur compounds: human and animal studies. J Nutr. 2001. 131:989S–993S.

44. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006. 17:4–12.

45. Moschen AR, Molnar C, Geiger S, Graziadei I, Ebenbichler CF, Weiss H, Kaser S, Kaser A, Tilg H. Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression. Gut. 2010. 59:1259–1264.

46. Hodge G, Hodge S, Han P. Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease. Cytometry. 2002. 48:209–215.

47. Colín-González AL, Ortiz-Plata A, Villeda-Hernández J, Barrera D, Molina-Jijón E, Pedraza-Chaverrí J, Maldonado PD. Aged garlic extract attenuates cerebral damage and cyclooxygenase-2 induction after ischemia and reperfusion in rats. Plant Foods Hum Nutr. 2011. 66:348–354.

48. Glatz JF, de Groot RH, Hesselink MK, Schrauwen P. Lipids in metabolic health and disease. Prostaglandins Leukot Essent Fatty Acids. 2011. 85:195.

49. Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol. 2005. 98:1154–1162.