The Effects of Dietary Interventions on mRNA Expression of Peroxisome Proliferator Activated Receptor Isoforms (PPAR Isoforms) in Rat Skeletal Muscle

장기간의 고지방 식이 섭취가 골격근 내 PPAR Isoforms 유전자 발현에 미치는 영향

  • Lee, Jang-Kyu (Division of Lifetime Sports and Leisure, Sangmyung University) ;
  • Kim, Jung-Kyu (Department of Leisure Sports, College of Humanities & Social Sciences, Kangwon National University) ;
  • Moon, Hee-Won (Department of Physical Education, College of Arts & Physical Education, Kangneung National University) ;
  • Shin, Young-Oh (Sport Medicine Laboratory, Korea National Sport University) ;
  • Lee, Jong-Sam (Department of Physical Education, Daegu University)
  • Published : 2007.04.30

Abstract

We determined the effects of dietary manipulations on messenger RNA of peroxisome proliferators activated receptor isoforms (i.e., PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$) in red vastus lateralis muscle of rats. Total 16 male Sprague-Dawley rats were used, and animals were divided into one of two dietary conditions: either chow diet group (CHOW; n=8) in which animals were 134 with standard rodent chow (61.8% carbohydrate, 15.7% fat, 22.5% protein) or high fat diet group (FAT n=8) in which animals were fed 24.3% carbohydrate, 52.8% fat, 22.9% protein. At the end of the 8 weeks of experimental period, red vastus lateralis muscle was dissected out from all animals, and PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$ mRNA expression was determined. There was no significant difference in body mass (BM) between CHOW and FAT. As expected, blood glucose and free fatty acid (FFA) concentration was higher in FAT than CHOW (p<0.05), and lactate concentration was significantly lower in FAT compared to CHOW (p<0.05). Insulin concentration tended to higher in FAT than CHOW ($67.2{\pm}21.9\;vs.\;27.0{\pm}5.2$ pmol/L), but it did not reach to the statistical significance. Gene expression of PPAR ${\alpha}$ was not significantly different between CHOW and FAT. It was not also significantly different in PPAR ${\beta}/{\delta}$. Interestingly, expression of mRNA in PPAR ${\gamma}$ however, was markedly depressed in FAT compared to CHOW (approximately 3 fold higher in CHOW; p<0.05). Results obtained from present study implies that PPAR ${\gamma}$ (as compensatory function of PPAR ${\alpha}$ is expressed) possibly exerts another major tuning roles in fatty acid transport, utilization, as well as biosynthesis in skeletal muscle cells. The situations and conditions that can be postulated for this implication need to be further examined.

Keywords

References

  1. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990; 347: 625-650
  2. Gilde AJ, Van Bilsen M. Peroxisome proliferators activated receptors (PPARS): regulators of gene expression in heart and skeletal muscle. Acta Physiol Scand 2003; 178: 425-434 https://doi.org/10.1046/j.1365-201X.2003.01161.x
  3. McAinch AJ, Lee JS, Burce CR, Tunstall RJ, Hawley JA, Cameron- Smith D. Dietary regulation of fat oxidative gene expression in different skeletal muscle fiber types. Obesity Res 2003; 11: 1471-1479 https://doi.org/10.1038/oby.2003.197
  4. Van Der Lee KA, Willemsen PH, Van Der Vusse GJ, Van Bilsen M. Effect of fatty acids on uncoupling protein 2 expression in the rat heart. FASEB J 2000; 14(3): 495-502 https://doi.org/10.1096/fasebj.14.3.495
  5. Wu P, Peters JM, Harris RA. Adaptive increase in pyruvate dehydrogenase kinase 4 during starvation is medicated by peroxisome proliferators-activated receptor alpha. Biochem Biophys Res Commun 2001; 287(2): 391-396 https://doi.org/10.1006/bbrc.2001.5608
  6. Young ME, Goodwin GW, Ying J, Guthrie P, Wilson CR, Laws FA, Taegtmeyer H. Regulation of cardiac and skeletal muscle malonyl CoA decarboxylase by fatty acids. Am J Physiol Endocrinol Metab 2001; 280(3): E471-E479
  7. Gorla-Bajszczak A, Siegrist-Kaiser C, Boss O, Burger AG, Meier CA. Expression of peroxisome proliferators activated receptors in lean and obese Zucker rats. Eur J Endocrinol 2000; 142: 71-78 https://doi.org/10.1530/eje.0.1420071
  8. Spiegelman BM. $PPAR-\gamma$ : Adipogenic regulator and thiazolidinedione receptor. Diabetes 1998; 47: 507-514 https://doi.org/10.2337/diabetes.47.4.507
  9. Escher P, Braissant O, Basu-Modak S, Michalik L, Wahli W. Desvergne B. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology 2001; 142: 4195-4202 https://doi.org/10.1210/en.142.10.4195
  10. Vidal-Puig A, Considine RV, Rimenez-Linan M, Werman A, Pories WJ, Caro JF, Flier JS. Peroxisome proliferators activated receptor gene expression in human tissues. Effects of obesity, weight loss, andregulation by insulin and glucocorticoids. J Clin Invest 1997; 99(10): 2416-2422 https://doi.org/10.1172/JCI119424
  11. Park KS, Ciaraldi TP, Abrams-Carter L, Mudaliar S, Nikoulina SE, Henry RR. PPAR-gamma gene expression is elevated in skeletal muscle of obese and type II diabetic subjects. Diabetes 1997; 46(7): 1230-1234 https://doi.org/10.2337/diabetes.46.7.1230
  12. Zierath JR, Ryder JW, Doebber T, Woods J, Wu M, Ventre J, Li Z, McCrary C, Berger J, Zhang B, Moller DE. Role of skeletal muscle in thiazolidinedione insulin sensitizer (PPARgamma agonist) action. Endocrinology 1998; 139(12): 5034-5041 https://doi.org/10.1210/en.139.12.5034
  13. Cresci S, Wright LD, Spratt JA, Briggs FN. Kelly DP. Activation of a novel metabolic gene regulatory pathway by chronic stimulation of skeletal muscle. Am J Physiol 1996; 270: C1413-C1420
  14. Feskens EJ, Virtanen SM, Rasanen L, Tuomilehto J, Stengard J, Pekkanen J, Nissinen A, Kromhout D. Dietary factors determining diabetes and impaired glucose tolerance. ['A 20 year follow']up of the Finnish and Dutch cohorts of the Seven Countries Study. Diabetes Care 1995; 18(8): 1104-1112 https://doi.org/10.2337/diacare.18.8.1104
  15. Delp MD, Duan C. Composition and size of type I, IIA, IID/X, and IIB fibers and citrate synthase activity of rat muscle. J Appl Physiol 1996; 80: 261-270 https://doi.org/10.1152/jappl.1996.80.1.261
  16. Lee JS, Bruce CR, Spriet LL, Hawley JA. Interaction of diet and training on endurance performance in rats. Exp Physiol 2001; 86(4): 499-508 https://doi.org/10.1113/eph8602158
  17. Storlien LH, Jenkins AB, Chisholm DJ, Pascoe WS, Khouri S, Kraegen EW. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and free fatty acids in muscle phospholipids. Diabetes 1991; 40: 280-289 https://doi.org/10.2337/diabetes.40.2.280
  18. Lee JS, Bruce CR, Tunstall RJ, Cameron-Smith D, Hugel H, Hawley JA. Interaction of exercise and diet on GLUT-4 protein and gene expression in Type I and Type II rat skeletal muscle. Acta Physiol Scand 2002; 175: 37-44 https://doi.org/10.1046/j.1365-201X.2002.00963.x
  19. Tunstall RJ, Mehan KA, Wadley GD, Collier GR, Bonen A, Hargreaves M, Cameron-Smith D. Exercise training increases lipid metabolism gene expression in human skeletal muscle. Am J Physiol Endocrinol Metab 2002; 283: E66-E72
  20. Muoio DM, MacLean PS, Lang DB, Li S, Houmard JA, Way JM, Winegar DA, Corton JC, Dohm GL, Kraus WE. Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferators-activated receptor (PPAR) ${\alpha}$ knockout mice: Evidence for compensatory regulation by PPAR ${delta}$. J Biol Chem 2002; 277(29): 26089-26097 https://doi.org/10.1074/jbc.M203997200
  21. Barger PM, Brandt JM, Leone TC, Weinheimer CJ Kelly DP. Deactivation of peroxisome proliferators-activated receptor-${\alpha}$ during cardiac hypertrophic growth. J Clin Invest 2000; 105: 1723-1730 https://doi.org/10.1172/JCI9056
  22. Barger PM, Browning AC, Garner AN, Kelly DP. p38 Mitogenactivated protein kinase activates peroxisome proliferators-activated receptor ${alpha}$: A potential role in the cardiac metabolic stress response. J Biol Chem 2001; 276(48): 44495-44502 https://doi.org/10.1074/jbc.M105945200
  23. Forman BM, Chen J, Evans RM. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferators-activated receptors ${alpha}$ and ${delta}$. Proc Natl Acad Sci USA 1997; 94: 4312-4317
  24. Lazennec G , Canaple L, Saugy D, Wahli W. Activation of peroxisome proliferators-activated receptors (PPARs) by their lignads and protein kinase A activators. Mol Endocrinol 2000; 14: 1962-1975 https://doi.org/10.1210/me.14.12.1962
  25. Su JL, Simmons CJ, Wisely B, Ellis B, Winegar DA. Monitoring of PPAR alpha protein expression in human tissue by the use of PPAR alpha-specific MAbs. Hybridoma 1998; 17(1): 47-53 https://doi.org/10.1089/hyb.1998.17.47
  26. Djouadi F, Brandt JM, Weinheimer CJ, Leone TC, Gonzalez FJ. Kelly DP. The role of the peroxisome proliferators-activated receptor alpha (PPAR alpha) in the control of cardiac lipid metabolism. Prostaglandins Leukot Essent Fatty Acids 1999; 60(5-6): 339-343 https://doi.org/10.1016/S0952-3278(99)80009-X
  27. Djouadi F, Weinheimer CJ, Saffitz JE, Pitchford C, Bastin J, Gonzalez FJ, Kelly DP. A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferators-activated receptor ${alpha}$-deficient mice. J Clin Invest 1998; 102: 1083-1091 https://doi.org/10.1172/JCI3949
  28. Leone TC, Weinheimer CJ, Kelly DP. A critical role for the peroxisome proliferators-activated receptor ${alpha}$ (PPAR ${alpha}$) in the cellular fasting response: The PPAR ${alpha}$-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci USA 1999; 96: 7473-7478
  29. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W. Peroxisome proliferators-activated receptor ${alpha}$ mediates the adaptive response to fasting. J Clin Invest 1999; 103: 1489-1498 https://doi.org/10.1172/JCI6223
  30. Horowitz JF, Leone TC, Feng W, Kelly DP, Klein S. Effect of endurance training on lipid metabolism in women: a potential role for PPAR${alpha}$ in the metabolic response to training. Am J Physiol Endocrinol Metab 2000; 279: E348-E355
  31. Muoio DM, Way JM, Tanner CJ, Winegar DA, Kliewer SA, Houmard JA, Kraus WE, Dohm GL. Peroxisome proliferators-activated receptor-${alpha}$ regulates fatty acid utilization in primary human skeletal muscle cells. Diabetes 2002; 51: 901-909 https://doi.org/10.2337/diabetes.51.4.901
  32. Jones PS, Savory R, Barratt P, Bell AR, Gray TJ, Jenkins NA, Gilbert DJ, Copeland NG, Bell DR. Chromosomal localization, inducibility, tissue-specific expression and strain differences in three murine peroxisome-proliferator-activated-recepotr genes. Eur J Biochem 1995; 233(1): 219-226 https://doi.org/10.1111/j.1432-1033.1995.219_1.x
  33. Barak Y, Lian D, He W, Ong ES, Nelson MC, Olefsky JM, Boland R, Evans RM. Effects of peroxisome proliferators-activated receptor ${delta}$ on placentation, adiposity, and colorectal cancer. PNAS 2002; 99(1): 303-308 https://doi.org/10.1073/pnas.012610299
  34. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 1999; 4(4): 611-617 https://doi.org/10.1016/S1097-2765(00)80211-7
  35. Unger RH, Orci L. Diseases of liporegulation: new perspective on obesity and related disorders. FASEB J 2001; 15: 312-321 https://doi.org/10.1096/fj.00-0590