Browse > Article
http://dx.doi.org/10.5352/JLS.2011.21.5.720

Inhibition of Adipocyte Differentiation and Adipogenesis by Aged Black Garlic Extracts in 3T3-L1 Preadipocytes  

Park, Jung-Ae (Blue-Bio Industry Regional Innovation Center, Dong-Eui University)
Park, Cheol (Blue-Bio Industry Regional Innovation Center, Dong-Eui University)
Han, Min-Ho (Department of Biomaterial Control, Graduate School, Dong-Eui University)
Kim, Byung-Woo (Blue-Bio Industry Regional Innovation Center, Dong-Eui University)
Chung, Yoon-Ho (Duksan B&F Co. LTD.)
Choi, Yung-Hyun (Blue-Bio Industry Regional Innovation Center, Dong-Eui University)
Publication Information
Journal of Life Science / v.21, no.5, 2011 , pp. 720-728 More about this Journal
Abstract
Garlic (Allium sativum) has been used as a source food as well as a traditional folk medicine ingredient since ancient times. Aged black garlic is a type of fermented garlic and is expected to have stronger anticancer and antioxidant activities than raw garlic. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis are poorly understood. In the present study, the effects and mechanisms of water extracts of raw garlic (WERG) and aged black garlic (WEABG) on adipocyte differentiation and adipogenesis in 3T3-L1 preadipocytes were investigated. Treatment with WEABG significantly suppressed terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner as confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining, however WERG had no such effect. In addition, WEABG reduced accumulation of cellular triglyceride, which is associated with a significant inhibition of key pro-adipogenic transcription factors including peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$), cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ (C/EBP${\alpha}$) and C/EBP${\beta}$. Taken together, these results provide important new insight that aged black garlic might inhibit adipogenesis by suppressing the pro-adipogenic transcription factors in 3T3-L1 preadipocytes, and further studies will be needed to identify the active compounds that confer the anti-obesity activity of aged black garlic.
Keywords
Aged black garlic; 3T3-L1 preadipocytes; PPAR${\gamma}$; C/EBP${\alpha}$; C/EBP${\beta}$;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 White, U. A. and J. M. Stephens. 2010. Transcriptional factors that promote formation of white adipose tissue. Mol. Cell Endocrinol. 318, 10-14.   DOI   ScienceOn
2 Wu, Z., P. Puigserver, and B. M. Spiegelman. 1999. Transcriptional activation of adipogenesis. Curr. Opin. Cell Biol. 11, 689-694.   DOI
3 Wyatt, S. B., K. P. Winters, and P. M. Dubbert. 2006. Overweight and obesity: prevalence, consequences, and causes of a growing public health problem. Am. J. Med. Sci. 331, 166-174.   DOI
4 Yano, T., S. Kobori, M. Sakai, Y. Anami, T. Matsumura, H. Matsuda, M. Kasho, and M. Shichiri. 1997. Beta-very low density lipoprotein induces triglyceride accumulation through receptor mediated endocytotic pathway in 3T3-L1 adipocytes. Atherosclerosis 135, 57-64.   DOI
5 Yeh, W. C., Z. Cao, M. Classon, and S. L. McKnight. 1995. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev. 9, 168-181.   DOI
6 Yeh, Y. Y. and S. M. Yeh. 1994. Garlic reduces plasma lipids by inhibiting hepatic cholesterol and triacylglycerol synthesis. Lipids 29, 189-193.   DOI
7 Zimmermann, R., J. G. Strauss, G. Haemmerle, G. Schoiswohl, R. Birner-Gruenberger, M. Riederer, A. Lass, G. Neuberger, F. Eisenhaber, A. Hermetter, and R. Zechner. 2004. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306, 1383-1386.   DOI
8 Rivlin, R. S. 2001. Historical perspective on the use of garlic. J. Nutr. 131, 951S-954S.
9 Roncari, D. A., D. C. Lau, and S. Kindler. 1981. Exaggerated replication in culture of adipocyte precursors from massively obese persons. Metabolism 30, 425-427.   DOI
10 Rosen, E. D. and O. A. MacDougald. 2006. Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 7, 885-896.   DOI
11 Spiegelman, B. M. and J. S. Flier. 2001. Obesity and the regulation of energy balance. Cell 104, 531-543.   DOI
12 Rosen, E. D. and B. M. Spiegelman. 2000. Molecular regulation of adipogenesis. Annu. Rev. Cell Dev. Biol. 16, 145-171.   DOI
13 Saltiel, A. R. and C. R. Kahn. 2001. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414, 799-806.   DOI
14 Schoonjans, K., B. Staels, and J. Auwerx. 1996. The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim. Biophys. Acta 1302, 93-109.   DOI   ScienceOn
15 Thomson, M. and M. Ali. 2003. Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent. Curr. Cancer Drug Targets 3, 67-81.   DOI
16 Vazquez-Vela, M. E., N. Torres, and A. R. Tovar. 2008. White adipose tissue as endocrine organ and its role in obesity. Arch. Med. Res. 39, 715-728.   DOI
17 Wang, N. D., M. J. Finegold, A. Bradley, C. N. Ou, S. V. Abdelsayed, M. D. Wilde, L. R. Taylor, D. R. Wilson, and G. I. Darlington. 1995. Impaired energy homeostasis in C/EBP alpha knockout mice. Science 269, 1108-1112.   DOI   ScienceOn
18 Wellman, N. S. and B. Friedberg. 2002. Causes and consequences of adult obesity: health, social and economic impacts in the United States. Asia Pac. J. Clin. Nutr. 11, S705-709.   DOI   ScienceOn
19 Hodge, G., S. Hodge, and P. Han. 2002. Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease. Cytometry 48, 209-215.   DOI
20 Jessen, B. A. and G. J. Stevens. 2002. Expression profiling during adipocyte differentiation of 3T3-L1 fibroblasts. Gene 299, 95-100.   DOI   ScienceOn
21 Kumaraguruparan, R., K. V. Chandra Mohan, S. K. Abraham, and S. Nagini. 2005. Attenuation of N-methyl- N'-nitro-N-nitrosoguanidine induced genotoxicity and oxidative stress by tomato and garlic combination. Life Sci. 76, 2247-2255.   DOI
22 Labreuche, J., P. J. Touboul, and P. Amarenco. 2009. Plasma triglyceride levels and risk of stroke and carotid atherosclerosis: a systematic review of the epidemiological studies. Atherosclerosis 203, 331-345.   DOI   ScienceOn
23 Lafontan, M. and D. Langin. 2009. Lipolysis and lipid mobilization in human adipose tissue. Prog. Lipid Res. 48, 275-297.   DOI
24 Lee, Y. M., O. C. Gweon, Y. J. Seo, J. Im, M. J. Kang, M. J. Kim, and J. I. Kim. 2009. Antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes mellitus. Nutr. Res. Pract. 3, 156-161.   DOI
25 Manickam, E., A. J. Sinclair, and D. Cameron-Smith. 2010. Suppressive actions of eicosapentaenoic acid on lipid droplet formation in 3T3-L1 adipocytes. Lipids Health Dis. 9, 57.   DOI
26 Patya, M., M. A. Zahalka, A. Vanichkin, A. Rabinkov, T. Miron, D. Mirelman, M. Wilchek, H. M. Lander, and A. Novogrodsky. 2004. Allicin stimulates lymphocytes and elicits an antitumor effect: a possible role of p21ras. Int. Immunol. 16, 275-281.   DOI
27 Qidwai, W., R. Qureshi, S. H. Hasan, and S. I. Azam. 2000. Effect of dietary garlic (Allium Sativum) on the blood pressure in humans-a pilot study. J. Pak. Med. Assoc. 50, 204-207.
28 Galic, S., J. S. Oakhill, and G. R. Steinberg. 2010. Adipose tissue as an endocrine organ. Mol. Cell Endocrinol. 316, 129-139.   DOI
29 Fox, K. E., D. M. Fankell, P. F. Erickson, S. M. Majka, J. T. Crossno Jr, and D. J. Klemm. 2006. Depletion of cAMP-response element-binding protein/ATF1 inhibits adipogenic conversion of 3T3-L1 cells ectopically expressing CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, or PPAR gamma 2. J. Biol. Chem. 281, 40341-40353.   DOI
30 Freytag, S. O., D. L. Paielli, and J. D. Gilbert. 1994. Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells. Genes Dev. 8, 1654-1663.   DOI
31 Gesta, S., Y. H. Tseng, and C. R. Kahn. 2007. Developmental origin of fat: tracking obesity to its source. Cell 131, 242-256.   DOI
32 Green, H. and O. Kehinde. 1976. Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells. Cell 7, 105-113.   DOI
33 Green, H. and M. Meuth. 1974. An established pre-adipose cell line and its differentiation in culture. Cell 3, 127-133.   DOI
34 Hafiz, M. S., M. I. Arslan, S. Banarjee, and M. Obaidullah. 2004. Studies on serum triglyceride level in patients with myocardial infarction. Mymensingh. Med. J. 13, 185-187.
35 Hamm, J. K., B. H. Park, and S. R. Farmer. 2001. A role for C/EBPbeta in regulating peroxisome proliferatoractivated receptor gamma activity during adipogenesis in 3T3-L1 preadipocytes. J. Biol. Chem. 276, 18464-18471.   DOI
36 Heilbronn, L., S. R. Smith, and E. Ravussin. 2004. Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type II diabetes mellitus. Int. J. Obes. Relat. Metab. Disord. 28, S12-21.   DOI
37 Chen, H. C., and R. V. Farese Jr. 2000. DGAT and triglyceride synthesis: a new target for obesity treatment? Trends Cardiovasc. Med. 10, 188-192.   DOI
38 Bernlohr, D. A., M. A. Bolanowski, T. J. Kelly Jr, and M. D. Lane. 1985. Evidence for an increase in transcription of specific mRNAs during differentiation of 3T3-L1 preadipocytes. J. Biol. Chem. 260, 5563-5567.
39 Bordia, T., N. Mohammed, M. Thomson, and M. Ali. 1996. An evaluation of garlic and onion as antithrombotic agents. Prostaglandins Leukot. Essent. Fatty Acids 54, 183-186.   DOI
40 Canizares, P., I. Gracia, L. A. Gomez, C. Martin de Argila, L. de Rafael L, and A. Garcia. 2002. Optimization of Allium sativum solvent extraction for the inhibition of in vitro growth of Helicobacter pylori. Biotechnol. Prog. 18, 1227-1232.   DOI
41 Cowherd, R. M., R. E. Lyle, and R. E. McGehee Jr. 1999. Molecular regulation of adipocyte differentiation. Semin. Cell Dev. Biol. 10, 3-10.   DOI
42 Duane, W. C. 1997. Cholesterol metabolism in familial hypertriglyceridemia: effects of obesity versus triglyceride level. J. Lab. Clin. Med. 130, 635-642.   DOI
43 El-Demerdash, F. M., M. I. Yousef, and N. I. El-Naga. 2005. Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats. Food Chem. Toxicol. 43, 57-63.   DOI
44 El-Jack, A. K., J. K. Hamm, P. F. Pilch, and S. R. Farmer. 1999. Reconstitution of insulin-sensitive glucose transport in fibroblasts requires expression of both PPARgamma and C/EBPalpha. J. Biol. Chem. 274, 7946-7951.   DOI   ScienceOn
45 Farese, R. V. Jr, and T. C. Walther. 2009. Lipid droplets finally get a little R-E-S-P-E-C-T. Cell 139, 855-860.   DOI   ScienceOn
46 Alessi, M. C., H. R. Lijnen, D. Bastelica, and I. Juhan-Vague. 2003. Adipose tissue and atherothrombosis. Pathophysiol. Haemost. Thromb. 33, 290-297.   DOI   ScienceOn
47 Augusti, K. T. 1996. Therapeutic values of onion (Allium cepa L.) and garlic (Allium sativum L.). Indian. J. Exp. Biol. 34, 634-640.
48 Ahmadian, M., Y. Wang, and H. S. Sul. 2010. Lipolysis in adipocytes. Int. J. Biochem. Cell Biol. 42, 555-559.   DOI
49 Farmer, S. R. 2006. Transcriptional control of adipocyte formation. Cell Metab. 4, 263-273.   DOI
50 Ahmad, M. S., M. Pischetsrieder, and N. Ahmed. 2007. Aged garlic extract and S-allyl cysteine prevent formation of advanced glycation endproducts. Eur. J. Pharmacol. 561, 32-38.   DOI