Liver PPAR${\alpha}$ and UCP2 are Involved in the Regulation of Ovariectomy-Induced Adiposity and Steatosis by Swim Training

  • 투고 : 2010.12.10
  • 심사 : 2010.12.30
  • 발행 : 2010.12.31

초록

It is suggested that ovariectomy induces body weight gain primarily in the form of adipose tissue in rodents. Since liver peroxisome proliferator-activated receptor ${\alpha}$ (PPAR${\alpha}$) and uncoupling 2 (UCP2) are involved in the regulation of energy expenditure, it was investigated whether swim training regulates ovariectomy-induced adiposity and steatosis through liver PPAR${\alpha}$ and UCP2 activation in female ovariectomized mice, an animal model of postmenopausal women. Swim-trained mice had significantly decreased adipose tissue weights compared with sedentary control mice. Histological analysis showed that hepatic lipid accumulation was inhibited by swim training. Concomitantly, swim training significantly increased mRNA levels of PPAR${\alpha}$ and its target genes responsible for peroxisomal fatty acid ${\beta}$-oxidation, such as acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and thiolase in the liver. Moreover, swim training induced the mRNA expression of UCP2. These results suggest that swim training can effectively prevent adiposity and steatosis caused by ovariectomy, in part through activation of liver PPAR${\alpha}$ and UCP2 in female obese mice.

키워드

참고문헌

  1. Boss O, Hagen T, Lowell BB. Uncoupling proteins 2 and 3: potential regulators of mitochondrial energy metabolism. Diabetes 2000. 49: 143-156. https://doi.org/10.2337/diabetes.49.2.143
  2. Brook GA, Fahey TD, White TP. Human bioenergetics and its applications. Exerc Physiol. 1995.2: 151-158.
  3. Buemann B, Tremblay A. Effects of exercise training on abdominal obesity and related metabolic complications. Sports Med. 1996.21: 191-212. https://doi.org/10.2165/00007256-199621030-00004
  4. 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
  5. Costet P, Legendre C, More J, Edgar A, Galtier P, Pineau T. Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis. J Biol Chem. 1998. 273: 29577-29585. https://doi.org/10.1074/jbc.273.45.29577
  6. Couillard C, Maurege 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. Enevoldsen LH, Stalknecht B, Fluckey JD, Galbo H. Effect of exercise training on in vivo insulin-stimulated glucose uptake in intra-abdominal adipose tissue in rats. Am J Physiol Endocrinol Metab. 2000. 278: E25-E34.
  8. Gasse C, Hense HW, Stieber J, Doring A, Liese AD, Keil U. Assessing hypertension management in the community: trends of prevalence, detection, treatment, and control of hypertension in the MONICA Project, Augsburg 1984-1995. J Hum Hypertens. 2001. 15: 27-36. https://doi.org/10.1038/sj.jhh.1001120
  9. Guerre-Millo M, Gervois P, Raspe E, Madsen L, Poulain P, Derudas B, Herbert JM, Winegar DA, Willson TM, Fruchart JC, Berge RK, Staels B. Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000. 275: 16638-16642. https://doi.org/10.1074/jbc.275.22.16638
  10. Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS. Increased adipose tissue in male and female estrogen receptoralpha knockout mice. Proc Natl Acad Sci USA. 2000. 97: 12729-12734. https://doi.org/10.1073/pnas.97.23.12729
  11. Horowitz JF, Leone TC, Feng W, Kelly DP, S. Klein S. Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training. Am J Physiol Endocrinol Metab. 2000. 279: E348-E355.
  12. 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
  13. 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 2004. 53: 607-613. https://doi.org/10.1016/j.metabol.2003.12.010
  14. 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
  15. Kissebah AH. Central obesity: measurement and metabolic effects. Diabetes Reviews 1997.5: 8-20.
  16. Lentes KU, Tu N, Chen H, Winnikes U, Reinert I, Marmann G, Pirke KM. Genomic organization and mutational analysis of the human UCP2 gene, a prime candidate gene for human obesity. J Recept Signal Transduct Res. 1999. 19: 229-244. https://doi.org/10.3109/10799899909036648
  17. 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
  18. Mystkowski P, Schwartz MW. Gonadal steroids and energy homeostasis in the leptin era. Nutrition 2000. 16: 937-946. https://doi.org/10.1016/S0899-9007(00)00458-5
  19. Nakatani T, Tsuboyama-Kasaoka N, Takahashi M, Miura S, Ezaki O. Mechanism for peroxisome proliferator-activated receptoralpha activator-induced up-regulation of UCP2 mRNA in rodent hepatocytes. J Biol Chem. 2002. 277: 9562-9569. https://doi.org/10.1074/jbc.M110132200
  20. Oh KS, Kim M, Lee J, Kim MJ, Nam YS, Ham JE, Shin SS, Lee CM, Yoon M. Liver PPARalpha and UCP2 are involved in the regulation of obesity and lipid metabolism by swim training in genetically obese db/db mice. Biochem Biophys Res Commun. 2006. 345: 1232-1239.
  21. Oh KS, Kim EY, Yoon M, Lee CM. Swim training improves leptin receptor deficiency-induced obesity and lipid disorder by activating uncoupling proteins. Exp Mol Med. 2007. 39: 385-394. https://doi.org/10.1038/emm.2007.43
  22. Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med. 2003.163: 427-436. https://doi.org/10.1001/archinte.163.4.427
  23. Pilote L, Dasgupta K, Guru V, Humphries KH, McGrath J, Norris C, Rabi D, Tremblay J, Alamian A, Barnett T, Cox J, Ghali WA, Grace S, Hamet P, Ho T, Kirkland S, Lambert M, Libersan D, O'Loughlin J, Paradis G, Petrovich M, Taga1akis V. A comprehensive view of sex-specific issues related to cardiovascular disease. CMAJ. 2007.176: S1-S44
  24. Rossi R, Nuzzo A, Origliani G, Modena MG Metabolic syndrome affects cardiovascular risk profile and response to treatment in hypertensive postmenopausal women. Hypertension 2008. 52: 865-872. https://doi.org/10.1161/HYPERTENSIONAHA.108.110478
  25. Shimizugawa T, Ono M, Shimamura M, Yoshida K, Ando Y, Koishi R, Ueda K, Inaba T, Minekura H, Koharna T, Furukawa H. ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of lipoprotein lipase. J Biol Chem. 2002. 277: 33742-33748. https://doi.org/10.1074/jbc.M203215200
  26. Siri P, Candela N, Zhang YL, Ko C, Eusufzai S, Ginsberg HN, Huang LS. Post-transcriptional stimulation of the assembly and secretion of triglyceride-rich apolipoprotein B lipoproteins in a mouse with selective deficiency of brown adipose tissue, obesity, and insulin resistance. J Biol Chem. 2001. 276: 46064-4607. https://doi.org/10.1074/jbc.M108909200
  27. Svendsen OL, Hassager C, Christiansen C. Age- and menopauseassociated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry. Metabolism 1995. 44: 369-373. https://doi.org/10.1016/0026-0495(95)90168-X
  28. Taghibiglou C, Carpentier A, Van Iderstine SC, Chen B, Rudy D, Aiton A, Lewis GF, Adeli K. Mechanisms of hepatic very low density lipoprotein overproduction in insulin resistance. Evidence for enhanced lipoprotein assembly, reduced intracellular ApoB degradation, and increased microsomal triglyceride transfer protein in a fructose-fed hamster model. J Biol Chem. 2000. 275: 8416-8425. https://doi.org/10.1074/jbc.275.12.8416
  29. Tan YY, Gast Ge, van der Schouw YT. Gender differences in risk factors for coronary heart disease. Maturitas. 2010. 65: 149-160. https://doi.org/10.1016/j.maturitas.2009.09.023
  30. Tchernof A, Poehlman ET, Despres JP. Body fat distribution, the menopause transition, and hormone replacement therapy. Diabetes Metab. 2000. 26: 12-20.
  31. Walberg JL, Mole PA, Stem JS. Effect of swim training on development of obesity in the genetically obese rat. Am J Physiol. 1982.242: R204-R211.
  32. 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
  33. 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
  34. 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