Browse > Article
http://dx.doi.org/10.6116/kjh.2011.26.1.065

Molecular biologic mechanism of obesity by GGEx18  

Lee, Hee-Young (Dept. of Formula Science, College of Oriental Medicine and Research Institute of Oriental Medicine, Dongeui University)
Yoon, Ki-Hyeon (Dept. of Formula Science, College of Oriental Medicine and Research Institute of Oriental Medicine, Dongeui University)
Seo, Bu-Il (Department of Oriental Herbology, Daegu Haany University)
Park, Gyu-Ryeol (Department of Oriental Herbology, Daegu Haany University)
Yoon, Mi-Chung (Dept. of Life Sciences, Mokwon University)
Shen, Zhi-Bin (Dept. of Chemistry and Analysis of Traditional Chinese Medicine, College of Chinese Materia Medica, Guangdong Pharmaceutical University)
Cui, Hong-Hua (Dept. of Chemistry and Analysis of Traditional Chinese Medicine, College of Chinese Materia Medica, Guangdong Pharmaceutical University)
Shin, Soon-Shik (Dept. of Formula Science, College of Oriental Medicine and Research Institute of Oriental Medicine, Dongeui University)
Publication Information
The Korea Journal of Herbology / v.26, no.1, 2011 , pp. 65-74 More about this Journal
Abstract
Objectives : This study was undertaken to verify the modulation mechanism of Gyeongshingangjeehwan18 (GGEx18) in ob/ob male mice. Methods : Eight-week old mice (wild-type C57BL/6J and ob/ob) were used for all experiments. Wild-type C57BL/6J mice were used as lean control and obese ob/ob mice were randomly divided into 5 groups : obese control, GGEx15 (Ephedra sinica Stapf + Rheum palmatum L.), GGEx16 (Ephedra sinica Stapf + Laminaria japonica Aresch), GGEx17 (Rheum palmatum L. + Laminaria japonica Aresch), and GGEx18 (Ephedra sinica Stapf + Laminaria japonica Aresch + Rheum palmatum L.). After mice were treated with several kinds of GGEx for 11 weeks, the mRNA expression of peroxisome proliferator-activated receptor (PPAR) target genes and uncoupling protein (UCP) were measured. In addition, $PPAR{\alpha}$ and $PPAR{\beta}$ transactivation was examined in NMu2Li hepatocytes, C2C12 myocytes, and 3T3-L1 preadipocytes using transient transfection assays. Results : 1. Hepatic $PPAR{\alpha}$ target genes, such as ACOX and VLCAD mRNA levels were significantly increased by GGEx18 compared with obese controls. In skeletal muscle, LCAD mRNA expression was stimulated by GGEx16, GGEx17, and GGEx18, whereas MCAD mRNA expression by GGEx17 and GGEx18. $PPAR{\beta}$ target LPL mRNA levels were also increased by GGEx16, GGEx17, and GGEx18 in skeletal muscle, but adipose LPL mRNA levels were decreased. In addition, GGEx18 upregulated UCP mRNA expression in skeletal muslce. 2. $PPAR{\alpha}$ reporter gene expression was increased by GGEx18 in NMu2Li cells compared with vehicle. $PPAR{\alpha}$ and $PPAR{\beta}$ reporter activities were also increased by all GGEx treatments in C2C12 and 3T3-L1 cells. Conclusions : These results suggest that GGEx can act as $PPAR{\alpha}$ and $PPAR{\beta}$ activators, and that GGEx may regulate obesity by stimulating $PPAR{\alpha}$, $PPAR{\beta}$, and UCP activity. Of the 4 compositions, GGEx18 seems to be most effective in improving obesity and lipid disorders.
Keywords
Ob/Ob mouse; Gyeongshingangjeehwan18 (GGEx18); $PPAR{\alpha}$; $PPAR{\beta}$; obesity;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, et al. PPAR alpha and PPAR gamma activators direct a distinct tissue-specific transcriptional response via a PPRE in lipoprotein lipase gene. EMBO J. 1996 ; 15 : 5336-48.
2 Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nat Med. 2004 Apr ; 10(4) : 355-361.   DOI   ScienceOn
3 Tontonoz P, Hu E, Graves R, et al. The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonist and the antihyperglycemic activity of thiazolidinediones. J. Med. Chem 1996 ; 39 : 665-68.   DOI   ScienceOn
4 Hagen T, Zhang CY, Slieker LJ, Chung WK, Leibel RL, Lowell BB. Assessment of uncoupling activity of the human uncoupling protein 3 short form and three mutants of the uncoupling protein gene using a yeast heterologous expression system. FEBS Lett 1999 ; 454 : 201-206.   DOI   ScienceOn
5 Rosen E.D. et al. PPAR is required for differentiation of adipose tissue in vivo and in vitro. Mol. Cell 1999 ; 4 : 611-7.   DOI   ScienceOn
6 Braissant O, Foufelle F, Scotto C, et al. Differential expression of peroxisome proliferatoractivated receptors (PPARs) : tissue distribution of PPAR-alpha, -beta, and gamm$\alpha$ in the adult rat. Endocrinology 1996 ; 137 : 354-66.   DOI   ScienceOn
7 Auboeuf D, Rieusset J, Fajas L, et al. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver receptor alpha in humans. Diabetes 1997 ; 46 : 1319-27.   DOI   ScienceOn
8 Linton, M.F., Fazio, S.K. Re-emergence of fibrates in the management of dyslipidemia and cardiovascular risk. Curr. Atheroscler. 2000 ; Rep 2 : 29-35.   DOI   ScienceOn
9 Kopelman PG. Obesity as a medical problem. Nature. 2000 Apr 6 ; 404(6778) : 635-43.
10 윤기현, 이희영, 정양삼, 서부일, 박규열, 윤미정, 신순식. Ob/Ob 마우스에서 輕身降脂丸의 비만조절. 大韓本草學會誌 2010 ; 25(3) : 1-9.
11 Zurlo, F., Larson, K., Bogardus, C, & Ravussin, E.. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J. Clin. Invest. 1990 ; 86 : 1423-1427.   DOI
12 Fleury C. Neverova M, Collins S et al. Uncoupling protein 1 : A novel gene linked to obesity and hyperinsulinemia. Nat Genet 1997 ; 15 : 269-272.   DOI
13 Baumruk F, Flachs P, Horakova M, Floryk D, Kopecky J.. Transgenic UCP1 in white adipocytes modulates mitochondrial membrane potential. FEBS Lett 1999 ; 444 : 206-210.   DOI
14 Evas D, Minouchehr S, Hagemann G et al. Frequency of and interaction between polymorphisms in the beta 3-adrenergic receptor and in uncoupling proteins 1 and 2 and obesity in Germans. Int J Obes 2000 ; 24 : 1239-1245.   DOI
15 Bukwoiecki, L.J., Follea, N., Lupien, J. & Paradis, A.. Metabolic relationships between lipolysis and respiration in rat brown adipocytes. The role of long chain fatty acids as regulators of mitochondrial respiration and feedback inhibitors of lipolysis. J. Biol. Chem. 1981 ; 256 : 12840-12848.
16 Elbein SC, Leppert M, Hasstedt S. Uncoupling protein 2 region in chromosome 11q13 is not linked to markers of obesity in familial type 2 diabetes. Diabetes 1997 ; 46 : 2105-2107.   DOI
17 Enerback, S., Jacobsson, A., Simpson, E.M., Guerra, C., Yamashita, H., M.E. et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 1997 ; 387 : 90-94.   DOI   ScienceOn
18 C.B. Chan, P.E. MacDonald, M.C. Saleh, D.C. Johns, E. Marban, M.B. Wheeler. Overexpression of uncoupling protein 2 inhibits glucose-stimulated insulin secretion from rat islets. Diabetes 1999 ; 48 : 1482-1486.   DOI   ScienceOn
19 Cusin, I et al. Chronic central leptin infusion enhances insulin-stimulated glucose metabolism and favors the expression of uncoupling proteins. Diabetes. 1998 ; 249 : 107-110.
20 Himms-Hagen, J.. Brown adipose tissue thermogenesis and obesity. Prog. Lipid. Res. 1989 ; 28 : 67-115.   DOI   ScienceOn
21 Collins, S et al. Role of leptin in fat regulation. Nature 1996 ; 380 : 677.   DOI   ScienceOn
22 Oliver et al. A selective peroxisome proliferator-activated receptor $\delta$ agonist promotes reverse cholesterol transport. Proc. Natl. Acad. Sci. USA. 1999 ; 96 : 6102-6.   DOI   ScienceOn
23 Tontonoz P, Hu E, Devine J, et al. PPAR gamma2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol. Cell. Biol 1995 ; 15 : 351-7.   DOI
24 Sfeir Z, Ibrahimi A, Amri E, et al. Regulation of FAT/CD36 gene expression : further evidence in support of a role of the protein in fatty acid binding/transport. Prostaglandins Leukot. Essent. Fatty Acids 1997 ; 57 : 17-21.   DOI   ScienceOn
25 Lowell, B.B. et al. Development of obesity in transgenic mice after genetic ablation brown adipose tissue. Nature 1993 ; 366 : 740-742.   DOI   ScienceOn
26 Winegar, D.A.. Effects of fenofibrate on lipid parameters in obese rhesus monkeys. J. Lipid. Res. 2001 ; 42 : 1543-51.