Browse > Article
http://dx.doi.org/10.4162/nrp.2012.6.6.499

Resveratrol inhibits the protein expression of transcription factors related adipocyte differentiation and the activity of matrix metalloproteinase in mouse fibroblast 3T3-L1 preadipocytes  

Kang, Nam E (Department of Food and Nutrition, Eulji University)
Ha, Ae Wha (Department of Food Science and Nutrition, Dankook University)
Kim, Ji Young (Department of Food Science and Nutrition, Dankook University)
Kim, Woo Kyoung (Department of Food Science and Nutrition, Dankook University)
Publication Information
Nutrition Research and Practice / v.6, no.6, 2012 , pp. 499-504 More about this Journal
Abstract
This study attempted to investigate the effects of resveratrol on the differentiation of adipocytes. After cells were treated with various concentrations of resveratrol (0, 10, 20, and 40 ${\mu}mol/L$), adipocyte proliferation, the protein expression of transcription factors, and MMPs' activities were determined. Cell proliferation was inhibited more within 4 days of incubation (P<0.05), and lipid accumulation in adipocyte was significantly inhibited by 93.8%, 92.4% and 91.5%, respectively, after two days of 10, 20, and 40 ${\mu}mol/L$ resveratrol treatment (P<0.05). Six days of incubation with the three resveratrol concentrations caused a significantly decreases of 63%, 59.9%, and 25.1% GPDH activity as a dose-dependent response. The triglyceride concentration also decreased significantly with the increase of resveratrol concentration (P<0.05). The protein expression of CCAAT/enhancer-binding protein (C/$EBP{\beta}$) was decreased significantly by 56% and 30% while $PPAR{\gamma}$ was significantly reduced by 57% and 15% with resveratrol treatments of 20 and 40 ${\mu}mol/L$, respectively (P<0.05). The protein expression of C/$EBP{\alpha}$ was decreased by 83%, 74%, and 38% to increased dosage levels, with significance determined for this decrease from 20 ${\mu}mol/L$ of resveratrol. The protein expression of fatty acid binding protein (FABP4) was decreased significantly by 88%, 72%, and 46% with the increase of resveratrol concentration. The activity of MMP-2 was decreased significantly by 84%, 70%, and 63% while MMP-9 activity was decreased significantly by 74%, 62%, and 39% with the increased resveratrol concentrations of 10, 20, and 40 ${\mu}mol/L$, respectively (P<0.05).
Keywords
Adipocyte; resveratrol; transcription factor; matrix metalloproteinase; differentiation;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Hajra AK, Larkins LK, Das AK, Hemati N, Erickson RL, MacDougald OA. Induction of the peroxisomal glycerolipidsynthesizing enzymes during differentiation of 3T3-L1 adipocytes. Role in triacylglycerol synthesis. J Biol Chem 2000;275:9441-6.   DOI   ScienceOn
2 McCawley LJ, Matrisian LM. Matrix metalloproteinases: they're not just for matrix anymore! Curr Opin Cell Biol 2001;13: 534-40.   DOI   ScienceOn
3 Bouloumie A, Sengenes C, Portolan G, Galitzky J, Lafontan M. Adipocyte produces matrix metalloproteinases 2 and 9: involvement in adipose differentiation. Diabetes 2001;50:2080-6.   DOI   ScienceOn
4 Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiol Rev 1998;78:783-809.   DOI
5 Alexander CM, Selvarajan S, Mudgett J, Werb Z. Stromelysin-1 regulates adipogenesis during mammary gland involution. J Cell Biol 2001;152:693-703.   DOI   ScienceOn
6 Tomiyama K, Nakata H, Sasa H, Arimura S, Nishio E, Watanabe Y. Wortmannin, a specific phosphatidylinositol 3-kinase inhibitor, inhibits adipocytic differentiation of 3T3-L1 cells. Biochem Biophys Res Commun 1995;212:263-9.   DOI   ScienceOn
7 Wise LS, Green H. Participation of one isozyme of cytosolic glycerophosphate dehydrogenase in the adipose conversion of 3T3 cells. J Biol Chem 1979;254:273-5.
8 Vankoningsloo S, De Pauw A, Houbion A, Tejerina S, Demazy C, de Longueville F, Bertholet V, Renard P, Remacle J, Holvoet P, Raes M, Arnould T. CREB activation induced by mitochondrial dysfunction triggers triglyceride accumulation in 3T3-L1 preadipocytes. J Cell Sci 2006;119:1266-82.   DOI   ScienceOn
9 Na MH, Seo EY, Kim WK. Effects of alpha-lipoic acid on cell proliferation and apoptosis in MDA-MB-231 human breast cells. Nutr Res Pract 2009;3:265-71.   DOI   ScienceOn
10 Kwon SY, Kang KJ. The effect of conjugated linoleic acid isomers on the cell proliferation, apotosis and expressions of uncoupling protein (Ucp) genes during differentiation of 3T3-L1 preadipocytes. Korean J Nutr 2004;37:533-9.
11 Park HJ, Yang JY, Ambati S, Della-Fera MA, Hausman DB, Rayalam S, Baile CA. Combined effects of genistein, quercetin, and resveratrol in human and 3T3-L1 adipocytes. J Med Food 2008;11:773-83.   DOI   ScienceOn
12 Rayalam S, Yang JY, Ambati S, Della-Fera MA, Baile CA. Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res 2008;22:1367-71.   DOI   ScienceOn
13 Yang JY, Della-Fera MA, Rayalam S, Ambati S, Hartzell DL, Park HJ, Baile CA. Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci 2008;82:1032-9.   DOI   ScienceOn
14 Cho KJ, Moon HE, Moini H, Packer L, Yoon DY, Chung AS. Alpha-lipoic acid inhibits adipocyte differentiation by regulating pro-adipogenic transcription factors via mitogen-activated protein kinase pathways. J Biol Chem 2003;278:34823-33.   DOI   ScienceOn
15 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;15:5336-48.
16 Zhang XH, Huang B, Choi SK, Seo JS. Anti-obesity effect of resveratrol-amplified grape skin extracts on 3T3-L1 adipocytes differentiation. Nutr Res Pract 2012;6;286-93.   DOI   ScienceOn
17 Jeong YS, Jung HK, Cho KH, Youn KS, Hong JH. Anti-obesity effect of grape skin extract in 3T3-L1 adipocytes. Food Sci Biotechnol 2011;20:635-42.   DOI
18 Gao D, Zhang X, Jiang X, Peng Y, Huang W, Cheng G, Song L. Resveratrol reduces the elevated level of MMP-9 induced by cerebral ischemia-reperfusion in mice. Life Sci 2006;78:2564-70.   DOI   ScienceOn
19 Chen S, Xiao X, Feng X, Li W, Zhou N, Zheng L, Sun Y, Zhang Z, Zhu W. Resveratrol induces Sirt1-dependent apoptosis in 3T3-L1 preadipocytes by activating AMPK and suppressing AKT activity and survivin expression. J Nutr Biochem 2012;23: 1100-12.   DOI   ScienceOn
20 Crandall DL, Hausman GJ, Kral JG. A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives. Microcirculation 1997;4:211-32.   DOI   ScienceOn
21 Bhat KP, Pezzuto JM. Cancer chemopreventive activity of resveratrol. Ann N Y Acad Sci 2002;957:210-29.   DOI   ScienceOn
22 de la Lastra CA, Villegas I. Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem Soc Trans 2007;35:1156-60.   DOI   ScienceOn
23 Levi F, Pasche C, Lucchini F, Ghidoni R, Ferraroni M, La Vecchia C. Resveratrol and breast cancer risk. Eur J Cancer Prev 2005;14:139-42.   DOI   ScienceOn
24 Kopp P. Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the 'French paradox'? Eur J Endocrinol 1998;138:619-20.   DOI   ScienceOn
25 Ray PS, Maulik G, Cordis GA, Bertelli AA, Bertelli A, Das DK. The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radic Biol Med 1999; 27:160-9.   DOI   ScienceOn
26 Das S, Alagappan VK, Bagchi D, Sharma HS, Maulik N, Das DK. Coordinated induction of iNOS-VEGF-KDR-eNOS after resveratrol consumption: a potential mechanism for resveratrol preconditioning of the heart. Vascul Pharmacol 2005;42:281-9.   DOI   ScienceOn
27 Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a highcalorie diet. Nature 2006;444:337-42.   DOI   ScienceOn
28 Chen S, Li Z, Li W, Shan Z, Zhu W. Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Can J Physiol Pharmacol 2011;89:793-9.
29 Green H, Kehinde O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 1975;5:19-27.   DOI   ScienceOn
30 Szkudelska K, Nogowski L, Szkudelski T. Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytes. J Steroid Biochem Mol Biol 2009;113:17-24.   DOI   ScienceOn
31 Lee MS, Kim CT, Kim CJ, Cho YJ, Kim Y. Effects of Portulaca oleracea L. extract on lipolysis and hormone sensitive lipase (HSL) gene expression in 3T3-L1 adipocytes. Korean J Nutr 2006;39:742-7.
32 Kim MJ, Kim Y, Chung JH, Kim JW, Kim HK. The effect of caffeine on 3T3-L1 adipocyte differentiation : a nutrigenomical approach. Korean J Nutr 2005;38:649-55.
33 Chon JW, Sung JH, Hwang EJ, Park YK. Chlorella methanol extract reduces lipid accumulation in and increases the number of apoptotic 3T3-L1 cells. Ann N Y Acad Sci 2009;1171:183-9.   DOI   ScienceOn
34 World Health Organization; International Association for the Study of Obesity; International Obesity Task Force. The Asia- Pacific Perspective: Redefining Obesity and Its Treatment. Sydney: Health Communications; 2000. p.15-21.
35 Ministry of Health and Welfare. National Health and Nutrition Examination Survey Report 2010. Seoul: Ministry of Health and Welfare; 2010.
36 Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Näslund E, Britton T, Concha H, Hassan M, Ryden M, Frisen J, Arner P. Dynamics of fat cell turnover in humans. Nature 2008;453:783-7.   DOI   ScienceOn
37 Cao Z, Umek RM, McKnight SL. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev 1991;5:1538-52.   DOI   ScienceOn
38 Björntorp P. Fat cell distribution and metabolism. Ann N Y Acad Sci 1987;499:66-72.
39 Distel RJ, Robinson GS, Spiegelman BM. Fatty acid regulation of gene expression. Transcriptional and post-transcriptional mechanisms. J Biol Chem 1992;267:5937-41.