WBCEx1 Reduces Feeding Efficiency Ratio and Visceral Obesity in Obese Mice Induced by High Fat Diet

고지방식이 비만마우스에서 월비가출탕(越婢加朮湯)이 식이효율과 내장지방에 미치는 영향

  • An, Jeong-Ran (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dong-Eui University) ;
  • Kang, Yeon-Kyeong (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dong-Eui University) ;
  • Chang, Dong-Ho (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dong-Eui University) ;
  • Lee, In-Seon (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dong-Eui University) ;
  • Shin, Soon-Shik (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dong-Eui University) ;
  • Jeong, Hae-Gyeong (Dept. of Formula Science, College of Oriental Medicine & Research Institute of Oriental Medicine, Dong-Eui University) ;
  • Lee, Hee-Young (Dept. of Formula Science, College of Oriental Medicine & Research Institute of Oriental Medicine, Dong-Eui University) ;
  • Lee, Hye-Rim (Dept. of Formula Science, College of Oriental Medicine & Research Institute of Oriental Medicine, Dong-Eui University)
  • 안정란 (동의대학교 한의과대학 한방재활의학과 교실) ;
  • 강연경 (동의대학교 한의과대학 한방재활의학과 교실) ;
  • 장동호 (동의대학교 한의과대학 한방재활의학과 교실) ;
  • 이인선 (동의대학교 한의과대학 한방재활의학과 교실) ;
  • 신순식 (동의대학교 한의과대학 한방재활의학과 교실) ;
  • 정해경 (동의대학교 한의과대학 방제학 교실) ;
  • 이희영 (동의대학교 한의과대학 방제학 교실) ;
  • 이혜림 (동의대학교 한의과대학 방제학 교실)
  • Received : 2010.11.08
  • Accepted : 2010.11.20
  • Published : 2011.01.30

Abstract

Objectives : This study was undertaken to verify the effects of Wolbigachul-tang1(WBCEx1) on obesity using high fat diet-induced male mice and to investigate the molecular mechanisms involved. Methods : 8-week old C57BL/6 mice were divided into 5 groups; lean control, obese control, WBCEx1, 2, 3. After mice were treated with WBCEx1(water extract), 2(30% ethanol extract), 3(water extract; Ephedra sinica Stapf., Gypsum fibrosum) for 12 weeks, body weight gain, feeding efficiency ratio, plasma lipid and glucose metabolism, the messenger RNA(mRNA) expression of peroxisome proliferator activated receptor(PPAR)$\alpha$ target genes were measured. In addition, $PPAR{\alpha}$ target gene expression was examined in liver, white adipose tissue and skeletal muscle. Results : 1. WBCEx1-treated mice had significantly lower body weight gain and feeding efficiency ratio. 2. Consistent with the effects on body weight gain, WBCEx1 decreased the weights of epididymal and retroperitoneal white adipose tissue, inguinal subcutaneous adipose tissue, and brown adipose tissue. 3. WBCEx1 significantly decreased plasma triglyceride and total cholesterol levels. 4. The size of adipocytes were significantly decreased by WBCEx1, whereas the adipocyte number per unit area was increased. Hepatic lipid accumulation was decreased by WBCEx1. 5. WBCEx1 did not affect the mRNA expression of $PPAR{\alpha}$ target genes in liver, adipose tissue, and skeletal muscle. 6. Plasma asparate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatine concentrations were in the physiological range. Liver and kidney weights were significantly lower following WBCEx treatment compared with obese controls, indicating that WBCEx does not show any toxic effects on liver and kidney. Conclusions : These results suggest that WBCEx1-induced body weight reduction is associated with appetite control and mediated by a mechanism other than the activation of $PPAR{\alpha}$.

Keywords

Wolbigachul-tang;$PPAR{\alpha}$;Feeding efficiency ratio;Obesity

References

  1. 대한비만학회. 비만의 진단과 치료. 서울:고려의학. 2003:83.
  2. 정석희. 비만관련정보 획득방법에 관한 조사 연구. 한방재활의학과학회지. 1998;8(2):1-15.
  3. Kopelman PG. Obesity as a medical problem. Nature. 2000;404(6778):635-43. https://doi.org/10.1038/35007508
  4. 서울대학교의과대학내과학교실. 내과학. 서울:군자출판사. 1996:852-62.
  5. 郭靄春. 黃帝內經素問校注語譯. 1판. 天津:天津科學技術出版社. 1981:54, 87, 183, 194, 282.
  6. 허수영. 비만의 동서의학적 고찰과 치료. 한방재활의학과학회지. 1997;7(1):227-86.
  7. 李秋貴, 李文端. 金櫃要略湯證論治. 1판. 北京:中國科學技術出版社. 2000:517-20.
  8. 宗全和. 中醫方劑通釋 卷1. 石家庄:河北科學技術出版社. 1995:95-7, 245-7.
  9. 박웅덕, 이영종. 高콜레스테롤 食餌로 유도된 비만 흰쥐에 대한 越婢場의 효과. 동의생리병리학회지. 2005;19(2):466-74.
  10. 오창호. 비만억제자인 ${\alpha}$-MSH 유사체의 합성 및 약효분석(선약개발연구개발사업 최종보고서). 서울:보건복지부. 2003:21.
  11. Garrido-Polonio C, Garcia-Linares MC, Garcia -Arias MT, Lopez-Varela S, Garcia-Fernandez MC, Terpstra AH, Sanchez-Muniz FJ. Thermally oxidised sunflower-seed oil increases liver and serum peroxidation and modifies lipoprotein composition in rats. British Joutnal of Nutrition. 2004;92(2):257-65. https://doi.org/10.1079/BJN20041174
  12. 한방재활의학과학회. 한방재활의학과학. 서울:군자출판사. 2003:349-51, 353-4.
  13. 이종호. 비만증의 치료. 비만학회지. 1992;1(1):21.
  14. 김정연, 송용선. 비만에 대한 동서의학적 고찰. 동의물리요법과학회지. 1993;3(1):299-314.
  15. 張介賓. 張氏類經. 서울:成輔社. 1982:586.
  16. 李東垣. 東垣醫書十種. 서울:大成文化社. 1983:70.
  17. 劉河間. 劉河間三六書. 서울:成輔社. 1976:82.
  18. 신동준. 태음조위탕과 마황이 비만 백서의 렙틴에 미치는 영향. 상지대학교. 1999.
  19. Vansal SS, Dennis RF. Direct effects of ephedrine isomer on human ${\beta}$-adrenergic receptor subtypes. Biochem Pharm. 1999;58:807-10. https://doi.org/10.1016/S0006-2952(99)00152-5
  20. Gurley B. Extract versus herb: effect of formulation on the absorption rate of botanical ephedrine from dietary supplements containing Ephedra. The Drug Monit. 2000;22:497. https://doi.org/10.1097/00007691-200008000-00021
  21. Gurley BJ, Wang P, Gardener SF. Ephedrine-type alkaloid content of nutritional supplements containing Ephedra sinica(Ma-huang) as determined by high performance liquid chromatography. Journal of Pharmaceutical Sciences. 1998;87:1547-53. https://doi.org/10.1021/js9801844
  22. Gurley BJ, Gardener SF, White LM, Wang PL. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica(Ma-huang). The Drug Monit. 1998;20:439-45. https://doi.org/10.1097/00007691-199808000-00015
  23. Kliewer SA, Lehmann JM, Willson TM. Orphan nuclear receptors: shifting endocrinology into reverse. Science. 1999;284:757-60. https://doi.org/10.1126/science.284.5415.757
  24. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature. 2000;405:421-4. https://doi.org/10.1038/35013000
  25. Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nature Medicine. 2004;10:355-61. https://doi.org/10.1038/nm1025
  26. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipid and lipoprotein metabolism. Circulation. 1998;98 :2088-93. https://doi.org/10.1161/01.CIR.98.19.2088
  27. Hertz R, Bishara-Shieban J, Bar-Tana J. Mode of action of peroxisome proliferators as hypolipidemic drugs. Suppression of apolipoprotein C-III. The Journal of Biological Chemistry. 1995;270:13470-5. https://doi.org/10.1074/jbc.270.22.13470
  28. 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:S29-37. https://doi.org/10.1016/0021-9150(96)05854-6
  29. 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. The EMBO Journal. 1996;15:5336-48.
  30. 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. The Journal of Biological Chemistry. 1997;272:28210-7. https://doi.org/10.1074/jbc.272.45.28210
  31. 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. Proceedings of the National Academy Sciences of the United States of America. 1992;89:7541-5. https://doi.org/10.1073/pnas.89.16.7541
  32. Osumi T, Osada S, Tsukamoto T. Analysis of peroxisome proliferator- responsive enhancer of the rat acyl-CoA oxidase gene. Annals of the New York Academy of Sciences. 1996;804:202-3. https://doi.org/10.1111/j.1749-6632.1996.tb18617.x
  33. 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. Biochemical and Biophysical Research Communications. 2000;269:347-51. https://doi.org/10.1006/bbrc.2000.2249
  34. Hainline BE, Kahlenbeck DJ, Grant J, Strauss AW. Tissue specific and developrrenta1 expression of rat long-and medium-chain acyl-CoA dehydrogenases. Biochimica et Biophysica Acta. 1993;1216:460-8. https://doi.org/10.1016/0167-4781(93)90015-6
  35. Kroetz DL, Yook P, Costet P, Bianchi P, Pineau T. Peroxisome proliferator-activated receptor alpha controls the hepatic CYP4A induction adaptive response to starvation and diabetes. The Journal of Biological Chemistry. 1998;273:31581-9. https://doi.org/10.1074/jbc.273.47.31581
  36. Staels B, Auwerx J. Regulation of apo A-I gene expression by fibrates. Atherosclerosis. 1998;137:S19-23. https://doi.org/10.1016/S0021-9150(97)00313-4
  37. Vazquez M, Roglans N, Cabrero A, Rodriguez C, Adzet T, Alegret M, Sanchez RM, Laguna JC. Bezafibrate induces acyl-CoA oxidase mRNA levels and fatty acid peroxisomal ${\beta}$-oxidation in rat white adipose tissue. Molecular Cellular Biochemistry. 2001;216:71-8. https://doi.org/10.1023/A:1011060615234
  38. Cabrero A, Alegret M, Sanchez RM, Adzet T, Laguna JC, Vazquez M. Bezafibrate reduces mRNA levels of adipocyte markers and increases fatty acid oxidation in primary culture of adipocytes. Diabetes. 2001;50:1883-90. https://doi.org/10.2337/diabetes.50.8.1883
  39. Brun S, Carmona MC, Mampel T, Vinas O, Giralt M, Iglesias R, Villarroya F. Activators of peroxisome proliferator-activated receptor-alpha induce the expression of the uncoupling protein-3 gene in skeletal muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth. Diabetes. 1999;48:1217-22. https://doi.org/10.2337/diabetes.48.6.1217
  40. Cabrero A, Llaverias G, Roglans N, Alegret M, Sanchez R, Adzet T, Laguna JC, Vazquez M. Uncoupling protein-3 mRNA levels are increased in white adipose tissue and skeletal muscle of bezafibrate-treated rats. Biochemical and Biophysical Research Communications. 1999;260:547-56. https://doi.org/10.1006/bbrc.1999.0926