Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
권호 표지

Regulation of PPAR and SREBP-1C Through Exercise in White Adipose Tissue of Female C57BL/6J Mice

  • Received : 2012.07.17
  • Accepted : 2012.08.19
  • Published : 2012.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Previous study showed that swimming improved obesity but was not through $PPAR{\alpha}$ activation in liver and skeletal muscle in high fat diet-fed female mice with functioning ovaries as an animal model of obese premenopausal women. Thus, this study was aimed at investigation of the effects of swimming on the promotion of health and its molecular mechanism in adipose tissue of high fat diet-fed female mice. Eight-week-old female C57BL/6J mice were randomly divided into two groups (a non-swim control group and a swim group, n=8/group). Mice in the swim group swam for 2 h daily for 6 weeks in water bath with temperature of $35{\pm}1^{\circ}C$. All the animals received high fat diet (45% kcal fat) for 6 weeks. Reverse transcription-polymerase chain reaction was used to elucidate the molecular mechanism. Female mice subjected to swimming had significantly decreased body weight gain and white adipose tissue mass compared with the female control mice. Histological studies illustrated that swimming decreases the hepatic lipid accumulation. As expected, swimming did not affect the expression of mRNA levels of peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and $PPAR{\alpha}$ target genes responsible for mitochondrial fatty acid ${\beta}$-oxidation, such as carnitine palmitoyltransgerase-1 and medium chain acyl-CoA dehydrogenase in the white adipose tissue. However, mice that underwent 6-weeks of swimming exercise had decreased the mRNA expression of lipogenic genes, such as sterol regulatory element-binding proteins-1C and fatty acid synthase in comparison to sedentary control mice, with decreased $PPAR{\gamma}$ target genes involved in adipocyte-specific marker genes, such as adipocyte fatty acid binding protein and leptin in the white adipose tissue. These results suggest that swimming can effectively prevent obesity induced by high fat diet-fed, in part through down-regulation of adipogenesis and lipogenesis in white adipose tissue of female obese mice. Moreover, these results suggest that swimming maybe contributing the promotion of health through regulation of adipogenesis and lipogenesis in overweight premenopausal women.

Keywords

References

  1. Alonso-Vale MI, Peres SB, Vernochet C, Farmer SR, Lima FB. Adipocyte differentiation is inhibited by melatonin through the regulation of C/EBPbeta transcriptional activity. J Pineal Res. 2009. 47: 221-227. https://doi.org/10.1111/j.1600-079X.2009.00705.x
  2. Auwerx J, Schoonjans K, Fruchart JC, Staels B. Transcriptional control of triglyceride metabolism: fibrates and fatty acids change the expression of the LPL and apo C-III genes by activating the nuclear receptor PPAR. Atherosclerosis 1996. 124: S29-S37.
  3. Bertrand HA, Masoro EJ, Yu BP. Increasing adipocyte number as the basis for perirenal depot growth in adult rats. Science 1978. 201: 1234-1235. https://doi.org/10.1126/science.151328
  4. Bray GA. Risks of obesity. Endocrinol Metab Clin North Am. 2003. 32: 787-804. https://doi.org/10.1016/S0889-8529(03)00067-7
  5. Brook GA, Fahey TD, White TP. Human bioenergetics and its applications. Exerc Physiol. 1995. 2: 151-158.
  6. Couillard C, Mauriege P, Imbeault P, Prud'homme D, Nadeau A, Tremblay A, Bouchard C, Despres JP. Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia. Int J Obes Relat Metab Disord. 2000. 24: 782-788. https://doi.org/10.1038/sj.ijo.0801227
  7. Halpern A, Mancini MC. Treatment of obesity: an update on antiobesity medications. Obes Rev. 2003. 4: 25-42. https://doi.org/10.1046/j.1467-789X.2003.00083.x
  8. Hertz R, Bishara-Shieban J, Bar-Tana J. Mode of action of peroxisome proliferators as hypolipidemic drugs: suppression of apolipoprotein C-III. J Biol Chem. 1995. 270: 13470-13475. https://doi.org/10.1074/jbc.270.22.13470
  9. Hollenberg AN, Susulic VS, Madura JP, Zhang B, Moller DE, Tontonoz P, Sarraf P, Spiegelman BM, Lowell BB. Functional antagonism between CCAAT/Enhancer binding protein-alpha and peroxisome proliferator-activated receptor-gamma on the leptin promoter. J Biol Chem. 1997. 272: 5283-5290. https://doi.org/10.1074/jbc.272.8.5283
  10. Hwang CS, Mandrup S, MacDougald OA, Geiman DE, Lane MD. Transcriptional activation of the mouse obese (ob) gene by CCAAT/enhancer binding protein alpha. Proc Natl Acad Sci U S A. 1996. 93: 873-877. https://doi.org/10.1073/pnas.93.2.873
  11. Jensen MD. Is visceral fat involved in the pathogenesis of the metabolic syndrome? Human model. Obesity (Silver Spring). 2006. 14: 20S-24S. https://doi.org/10.1038/oby.2006.278
  12. Jeong S, Kim M, Han M, Lee H, Ahn J, Kim M, Song YH, Shin C, Nam KH, Kim TW, Oh GT, Yoon M. Fenofibrate prevents obesity and hypertriglyceridemia in low-density lipoprotein receptor-null mice. Metabolism 2004a. 53: 607-613. https://doi.org/10.1016/j.metabol.2003.12.010
  13. Jeong S, Han M, Lee H, Kim M, Kim J, Nicol CJ, Kim BH, Choi JH, Nam KH, Oh GT, Yoon M. Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice. Metabolism 2004b. 53: 1284-1289. https://doi.org/10.1016/j.metabol.2004.05.003
  14. Jeong S, Yoon M. Inhibition of the actions of peroxisome proliferator-activated receptor alpha on obesity by estrogen. Obesity (Silver Spring). 2007. 15: 1430-1440. https://doi.org/10.1038/oby.2007.171
  15. Jeong S, Yoon M. Differential regulation of Obesity by swim training in female Sham-operated and ovariectomized mice. J Exp Biomed Sci. 2011. 17: 13-20.
  16. Jun J, Lee WL, Lee YR, Jeong S. Swim training fitness in high fat diet-fed female mice. J Exp Biomed Sci. 2010. 16: 151-159.
  17. Kannisto K, Chibalin A, Glinghammar B, Zierath JR, Hamsten A, Ehrenborg E. Differential expression of peroxisomal proliferator activated receptors alpha and delta in skeletal muscle in response to changes in diet and exercise. Int J Mol Med. 2006. 17: 45-52.
  18. King GA, Fitzhugh EC, Bassett Jr DR, McLaughlin JE, Strath SJ, Swartz AM, Thompson DL. Relationship of leisure-time physical activity and occupational activity to the prevalence of obesity. Int J Obes Relat Metab Disord. 2001. 25: 606-612. https://doi.org/10.1038/sj.ijo.0801583
  19. Kissebah AH. Central obesity: measurement and metabolic effects. Diabetes Reviews. 1997. 5: 8-20.
  20. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, Lehmann JM. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A. 1997. 94: 4318-4323. https://doi.org/10.1073/pnas.94.9.4318
  21. Kubota N, Terauchi Y, Miki H, Tamemoto H, Yamauchi T, Komeda K, Satoh S, Nakano R, Ishii C, Sugiyama T, Eto K, Tsubamoto Y, Okuno A, Murakami K, Sekihara H, Hasegawa G, Naito M, Toyoshima Y, Tanaka S, Shiota K, Kitamura T, Fujita T, Ezaki O, Aizawa S, Kadowaki T. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell. 1999. 4: 597-609. https://doi.org/10.1016/S1097-2765(00)80210-5
  22. Kump DS, Booth FW. Sustained rise in triacylglycerol synthesis and increased epididymal fat mass when rats cease voluntary wheel running. J Physiol. 2005. 565: 911-925. https://doi.org/10.1113/jphysiol.2005.084525
  23. Martin G, Schoonjans K, Lefebvre AM, Staels B, Auwerx J. Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. J Biol Chem. 1997. 272: 28210-28217. https://doi.org/10.1074/jbc.272.45.28210
  24. Mochizuki K, Suruga K, Fukami H, Kiso Y, Takase S, Goda T. Selectivity of fatty acid ligands for PPARalpha which correlates both with binding to cis-element and DNA bindingindependent transactivity in Caco-2 cells. Life Sci. 2006. 80: 140-145. https://doi.org/10.1016/j.lfs.2006.08.029
  25. Morifuji M, Sanbongi C, Sugiura K. Dietary soya protein intake and exercise training have an additive effect on skeletal muscle fatty acid oxidation enzyme activities and mRNA levels in rats. Br J Nutr. 2006. 96: 469-475.
  26. Mougios V, Ring S, Petridou A, Nikolaidis MG. Duration of coffee- and exercise-induced changes in the fatty acid profile of human serum. J Appl Physiol. 2003. 94: 476-484.
  27. Muller MJ, Mast M, Asbeck I, Langnäse K, Grund A. Prevention of obesity--is it possible? Obes Rev. 2001. 2: 15-28. https://doi.org/10.1046/j.1467-789x.2001.00012.x
  28. Nicolas-Frances V, Dasari VK, Abruzzi E, Osumi T, Latrufle N. The peroxisome proliferator response element (PPRE) present at positions -681/-669 in the rat liver 3-ketoacyl-CoA thiolase B gene functionally interacts differently with PPARalpha and HNF-4. Biochem Biophys Res Commun. 2000. 269: 347-351. https://doi.org/10.1006/bbrc.2000.2249
  29. Ogawa R, Mizuno H, Watanabe, Migita M, Hyakusoku H, Shimada T. Adipogenic differentiation by adipose-derived stem cell harvested from GFP transgenic mice-including relationship of sex differences. Biochem Biophys Res Commun. 2004. 319: 511-517. https://doi.org/10.1016/j.bbrc.2004.05.021
  30. Osumi T, Osada S, Tsukamoto T. Analysis of peroxisome proliferator-responsive enhancer of the rat acyl-CoA oxidase gene. Ann N Y Acad Sci. 1996. 804: 202-213. https://doi.org/10.1111/j.1749-6632.1996.tb18617.x
  31. Pedersen BK, Saltin B. Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports. 2006. 16: 3-63. https://doi.org/10.1111/j.1600-0838.2006.00520.x
  32. Petridou A, Tsalouhidou S, Tsalis G, Schulz T, Michna H, Mougios V. Long-term exercise increases the DNA binding activity of peroxisome proliferator-activated receptor gamma in rat adipose tissue. Metabolism. 2007. 56: 1029-1036. https://doi.org/10.1016/j.metabol.2007.03.011
  33. Pighon A, Gutkowska J, Jankowski M, Rabasa-Lhoret R, Lavoie JM. Exercise training in ovariectomized rats stimulates estrogenic-like effects on expression of genes involved in lipid accumulation and subclinical inflammation in liver. Metabolism. 2011. 60: 629-639. https://doi.org/10.1016/j.metabol.2010.06.012
  34. Redinger RN. Is enhanced energy utilization the answer to prevention of excessive adiposity? J Ky Med Assoc. 2009. 107: 211-217.
  35. Rogge MM. The role of impaired mitochondrial lipid oxidation in obesity. Biol Res Nurs. 2009. 10: 356-373. https://doi.org/10.1177/1099800408329408
  36. 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: 611-617. https://doi.org/10.1016/S1097-2765(00)80211-7
  37. Rosen ED, Waikey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev. 2000. 14: 1293-1307.
  38. Saltin B, Pilegaard H. Metabolic fitness: physical activity and health. Ugeskr Laeger. 2002. 164: 2156-2162.
  39. Sander K, Beatrice D, Walter W. Roles of PPARs in health and disease. Nature 2000. 405: 421-424. https://doi.org/10.1038/35013000
  40. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs M, Deeb S, Staels B, Auwerx J. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 1996. 15: 5336-5348.
  41. Schoonjans K, Staels B, Auwerx J. Role of peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res. 2000. 37: 907-925.
  42. Semple RK, Chatterjee VK, O'Rahilly S. PPARgamma and human metabolic disease. J Clin Invest. 2006. 116: 581-589. https://doi.org/10.1172/JCI28003
  43. Shimano H, Horton JD, Hammer RE, Shimomura I, Brown MS, Goldstein JL. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J Clin Invest. 1996. 98: 1575-1584. https://doi.org/10.1172/JCI118951
  44. Shimano H, Horton JD, Shimomura I, Hammer RE, Brown MS, Goldstein JL. Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. J Clin Invest. 1997. 99: 846-854. https://doi.org/10.1172/JCI119248
  45. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrate on lipid and lipoprotein metabolism. Circulation 1998. 98: 2088-2093. https://doi.org/10.1161/01.CIR.98.19.2088
  46. Swinburn B, Egger G. Preventive strategies against weight gain and obesity. Obes Rev. 2002. 3: 289-301. https://doi.org/10.1046/j.1467-789X.2002.00082.x
  47. Tang QQ, Zhang JW, Daniel Lane M. Sequential gene promoter interactions by C/EBPbeta, C/EBPalpha, and PPARgamma during adipogenesis. Biochem Biophys Res Commun. 2004. 318: 213-218. https://doi.org/10.1016/j.bbrc.2004.04.017
  48. Thompson DL, Townsend KM, Boughey R, Patterson K, Bassett DR Jr. Substrate use during and following moderate- and low-intensity exercise: Implications for weight control. Eur J Appl Physiol Occup Physiol. 1998. 78: 43-49. https://doi.org/10.1007/s004210050385
  49. Vazquez-Vela ME, Torres N, Tovar AR. White adipose tissue as endocrine organ and its role in obesity. Arch Med Res. 2008. 39: 715-728. https://doi.org/10.1016/j.arcmed.2008.09.005
  50. Villena JA, Viollet B, Andreelli F, Kahn A, Vaulont S, Sul HS. Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit. Diabetes. 2004. 53: 2242-2249. https://doi.org/10.2337/diabetes.53.9.2242
  51. Yagi K, Kondo D, Okazaki Y, Kano K. A novel preadipocyte cell line established from mouse adult mature adipocytes. Biochem Biophys Res Commun. 2004. 321: 967-974. https://doi.org/10.1016/j.bbrc.2004.07.055
  52. Wang X, Kilgore MW. Signal cross-talk between estrogen receptor alpha and beta and the peroxisome proliferator-activated receptor gamma1 in MDA-MB-231 and MCF-7 breast cancer cells. Mol Cell Endocrinol 2002. 194: 123-133. https://doi.org/10.1016/S0303-7207(02)00154-5
  53. Wier LT, Ayers GW, Jackson AS, Rossum AC, Carlos Poston WS, Foreyt JP. Determining the amount of physical activity needed for long-term weight control. Int J Obes Relat Metab Disord. 2001. 25: 613-621. https://doi.org/10.1038/sj.ijo.0801586
  54. Yoon M, Jeong S, Nicol CJ, Lee H, Han M, Kim JJ, Seo YJ, Ryu C, Oh GT. Fenofibrate regulates obesity and lipid metabolism with sexual dimorphism. Exp Mol Med. 2002. 34: 481-488. https://doi.org/10.1038/emm.2002.67
  55. Yoon M, Jeong S, Lee H, Han M, Kang JH, Kim EY, Kim M, Oh GT. Fenofibrate improves lipid metabolism and obesity in ovariectomized LDL receptor-null mice. Biochem Biophys Res Commun. 2003. 302: 29-34. https://doi.org/10.1016/S0006-291X(03)00088-3
  56. Zhang B, Marcus SL, Sajjadi FG, Alvares K, Reddy JK, Subramani S, Rachubinski RA, Capone JP. Identification of a peroxisome proliferator-responsive element upstream of the gene encoding rat peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase. Proc Natl Acad Sci USA. 1992. 89: 7541-7545. https://doi.org/10.1073/pnas.89.16.7541