DOI QR코드

DOI QR Code

Fenofibrate Reduces Age-related Hypercholesterolemia in Normal Rats on a Standard Diet

  • Han, Ying (Departments of Pharmacology, Dong-A University College of Medicine, Medical Science Research Center) ;
  • Do, Mi-Hyang (Departments of Pharmacology, Dong-A University College of Medicine, Medical Science Research Center) ;
  • Kim, Mi-Sun (Departments of Pharmacology, Dong-A University College of Medicine, Medical Science Research Center) ;
  • Seo, Eun-Hui (Departments of Pharmacology, Dong-A University College of Medicine, Medical Science Research Center) ;
  • Park, Mi-Kyoung (Departments of Internal Medicine, Dong-A University College of Medicine, Medical Science Research Center) ;
  • Kim, Duk Kyu (Departments of Internal Medicine, Dong-A University College of Medicine, Medical Science Research Center) ;
  • Lee, Hye-Jeong (Departments of Pharmacology, Dong-A University College of Medicine, Medical Science Research Center) ;
  • Seo, Su-Yeong (Departments of Microbiology, Dong-A University College of Medicine, Medical Science Research Center)
  • Received : 2010.03.09
  • Accepted : 2010.04.16
  • Published : 2010.04.30

Abstract

Plasma cholesterol is increased in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol and decreased receptor-mediated clearance of plasma low-density lipoprotein (LDL) cholesterol. The aims of this study were: (1) to determine age-related changes in plasma lipid profiles, and (2) to determine the effect of fenofibrate, an activator of peroxisome proliferator activated receptor alpha (PPAR $\alpha$), on plasma lipid profiles in normal rats on a standard diet. Male Sprague-Dawley (SD) rats (n=15) were fed standard chow and water from 10 to 25 weeks of age. During that period, we measured daily food intake, body weight, fasting and random blood glucose levels, plasma total cholesterol (TC), triglycerides (TG), and free fatty acid (FFA) levels. At 20 weeks of age, all rats were randomly divided into two groups: a fenofibrate group (in which rats were gavaged with 300 mg/kg/day of fenofibrate) and a control group (gavaged with water). Fenofibrate treatment lasted 5 weeks. There were no significant changes in daily food intake, blood glucose, and plasma TG level with age. Body weight, plasma TC, and FFA levels were significantly increased with age. Fenofibrate significantly decreased plasma concentrations of TC and FFA, which had been increased with age. However, fenofibrate did not influence the plasma concentration of TG, which had not increased with age. These results suggest that fenofibrate might have a novel role in preventing age-related hypercholesterolemia in SD rats on a normal diet.

Acknowledgement

Supported by : Dong-A University

References

  1. Ericsson S, Eriksson M, Vitols S, Einarsson K, Berglund L, Angelin B. Influence of age on the metabolism of plasma low density lipoproteins in healthy males. J Clin Invest. 1991;87: 591-596. https://doi.org/10.1172/JCI115034
  2. Ericsson S, Berglund L, Frostegard J, Einarsson K, Angelin B. The influence of age on low density lipoprotein metabolism: effects of cholestyramine treatment in young and old healthy male subjects. J Intern Med. 1997;242:329-337. https://doi.org/10.1046/j.1365-2796.1997.00238.x
  3. Levine GN, Keaney JF Jr, Vita JA. Cholesterol reduction in cardiovascular disease: Clinical benefits and possible mechanisms. N Engl J Med. 1995;332:512-521. https://doi.org/10.1056/NEJM199502233320807
  4. Bays HR, Dujovne CA, Lansing AM. Drug treatment of dyslipidemias: Practical guidelines for the primary care physician. Heart Dis Stroke. 1992;1:357-365.
  5. Grundy SM, Cleeman JI, Rifkind BM, Kuller LH. Cholesterol lowering in the elderly population. Coordinating Committee of the National Cholesterol Education Program. Arch Intern Med. 1999;159:1670-1678. https://doi.org/10.1001/archinte.159.15.1670
  6. Trapani L, Violo F, Pallottini V. Hypercholesterolemia and 3-hydroxy-3-methylglutaryl coenzyme A reductase regulation in aged female rats. Exp Gerontol. 2010;45:119-128. https://doi.org/10.1016/j.exger.2009.10.014
  7. Willson TM, Wahli W. Peroxisome proliferator-activated receptor agonists. Curr Opin Chem Biol. 1997;1:235-241. https://doi.org/10.1016/S1367-5931(97)80015-4
  8. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347:645-650. https://doi.org/10.1038/347645a0
  9. Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab. 2004;89:463-478. https://doi.org/10.1210/jc.2003-030723
  10. Najib J. Fenofibrate in the treatment of dyslipidemia: a review of the data as they relate to the new suprabioavailable tablet formulation. Clin Ther. 2002;24:2022-2205. https://doi.org/10.1016/S0149-2918(02)80095-9
  11. Francis GA, Annicotte JS, Auwerx J. PPAR-alpha effects on the heart and other vascular tissues. Am J Physiol Heart Circ Physiol. 2003;285:1-9. https://doi.org/10.1152/ajpheart.01118.2002
  12. Chaput E, Saladin R, Silvestre M, Edgar AD. Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Biochem Biophys Res Commun. 2000;271:445-450. https://doi.org/10.1006/bbrc.2000.2647
  13. Mancini FP, Lanni A, Sabatino L, Moreno M, Giannino A, Contaldo F, Colantuoni V, Goglia F. Fenofibrate prevents and reduces body weight gain and adiposity in diet-induced obese rats. FEBS Lett. 2001;491:154-158. https://doi.org/10.1016/S0014-5793(01)02146-9
  14. Lee HJ, Choi SS, Park MK, An YJ, Seo SY, Kim MC, Hong SH, Hwang TH, Kang DY, Garber AJ, Kim DK. Fenofibrate lowers abdominal and skeletal adiposity and improves insulin sensitivity in OLETF rats. Biochem Biophys Res Commun. 2002;296:293-299. https://doi.org/10.1016/S0006-291X(02)00822-7
  15. Han Y, Joe Y, Seo E, Lee SR, Park MK, Lee HJ, Kim DK. The hyperleptinemia and ObRb expression in hyperphagic obese rats. Biochem Biophys Res Commun. 2010;394:70-74. https://doi.org/10.1016/j.bbrc.2010.02.104
  16. Kłosiewicz-Latoszek L, Szostak WB, Grzybowska B, Białobrzeska- Paluszkiewicz J, Wiśniewska B, Stolarska I. Comparison of combined statin-fibrate treatment to monotherapy in patients with mixed hyperlipidemia. Kardiol Pol. 2004;60:567-577.
  17. Krempf M, Rohmer V, Farnier M, Issa-Sayegh M, Corda C, Sirugue I, Gerlinger C, Masseyeff-Elbaz MF. Efficacy and safety of micronised fenofibrate in a randomised double-blind study comparing four doses from 200 mg to 400 mg daily with placebo in patients with hypercholesterolemia. Diabetes Metab. 2000;26: 184-191.
  18. Pallottini V, Martini C, Cavallini G, Donati A, Bergamini E, Notarnicola M,Caruso MG, Trentalance A. Modified HMG-CoA reductase and LDLr regulation is deeply involved in age-related hypercholesterolemia. J Cell Biochem. 2006;98:1044-1053. https://doi.org/10.1002/jcb.20951
  19. Kobayashi A, Suzuki Y, Kuno H, Sugai S, Sakakibara H, Shimoi K. Effects of fenofibrate on plasma and hepatic transaminase activities and hepatic transaminase gene expression in rats. J Toxicol Sci. 2009;34:377-387. https://doi.org/10.2131/jts.34.377
  20. Alvarez de Sotomayor M, Mingorance C, Andriantsitohaina R. Fenofibrate improves age-related endothelial dysfunction in rat resistance arteries. Atherosclerosis. 2007;193:112-120. https://doi.org/10.1016/j.atherosclerosis.2006.08.041