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Chitosan Oligosaccharides Inhibit Adipogenesis in 3T3-L1 Adipocytes  

Cho, Eun-Jae (Department of Biotechnology, Daegu University)
Rahman, Atiar (Department of Biotechnology, Daegu University)
Kim, Sang-Woo (Department of Biotechnology, Daegu University)
Baek, Yu-Mi (Department of Biotechnology, Daegu University)
Hwang, Hye-Jin (Department of Biotechnology, Daegu University)
Oh, Jung-Young (Department of Biotechnology, Daegu University)
Hwang, Hee-Sun (Department of Biotechnology, Daegu University)
Lee, Sung-Hak (Department of Biotechnology, Daegu University)
Yun, Jong-Won (Department of Biotechnology, Daegu University)
Publication Information
Journal of Microbiology and Biotechnology / v.18, no.1, 2008 , pp. 80-87 More about this Journal
Abstract
The 3T3-L1 cell line is a well-established and commonly used in vitro model to assess adipocyte differentiation. Over the course of several days, confluent 3T3-L1 cells can be converted to adipocytes in the presence of an adipogenic cocktail. In this study, the effects of chitosan oligosaccharides (CO) on adipocyte differentiation of 3T3-L1 cells were studied. The CO significantly decreased lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. The low molecular mass CO (1-3 kDa) were the most effective at inhibiting adipocyte differentiation. Moreover, mRNA expression levels of both CCAAT/enhancer-binding protein (C/EBP) ${\alpha}$ and peroxisome proliferator-activated receptor (PPAR) ${\gamma}$, the key adipogenic transcription factors, were markedly decreased by CO treatments. CO also significantly down regulated adipogenic marker proteins such as leptin, adiponectin, and resistin. Our results suggest a role for CO as antiobesity agents by inhibiting adipocyte differentiation mediated through the down regulated expression of adipogenic transcription factors and other specific genes.
Keywords
Adipocyte; chitosan oligosaccharide; obesity; 3T3-L1 cell$PPAR{\gamma}$$C/EBP{\alpha}$;
Citations & Related Records
Times Cited By KSCI : 6  (Citation Analysis)
Times Cited By Web Of Science : 25  (Related Records In Web of Science)
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1 Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248-254   DOI   ScienceOn
2 Fong, J. C., C. C. Chen, D. Liu, M. S. Tu, S. P. Chai, and Y. S. Kao. 1999. Synergistic effect of arachidonic acid and cyclic AMP on glucose transport in 3T3-L1 adipocytes. Cell. Signal. 11: 53-58   DOI   ScienceOn
3 Gallaher, D. D., C. M. Gallaher, G. J. Mahrt, T. P. Carr, C. H. Hollingshead, R. Hesslink Jr., and J. Wise. 2002. A glucomannan and chitosan fiber supplement decreases plasma cholesterol and increases cholesterol excretion in overweight normocholesterolemic humans. J. Am. Coll. Nutr. 21: 428-433   DOI
4 Green, H. and M. Meuth. 1974. An established pre-adipose cell line and its differentiation in culture. Cell 3: 127-133   DOI   ScienceOn
5 Janke, J., S. Engeli, K. Gorzelniak, F. C. Luft, and A. M. Sharma. 2002. Resistin gene expression in human adipocytes is not related to insulin resistance. Obesity Res. 10: 1-5   DOI
6 Jeon, T., S. G. Hwang, S. Hirai, T. Matsui, H. Yano, T. Kawada, B. O. Lim, and D. K. Park. 2004. Red yeast rice extracts suppress adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 cells. Life Sci. 75: 3195-3203   DOI   ScienceOn
7 Jessen, B. A. and G. J. Stevens. 2002. Expression profiling during adipocyte differentiation of 3T3-L1 fibroblasts. Gene 299: 95-100   DOI   ScienceOn
8 Kim, J. H., D. H. Hahm, D. C. Yang, J. H. Kim, H. J. Lee, and I. Shim. 2005. Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat. J. Pharmacol. Sci. 97: 124-131   DOI   ScienceOn
9 Kim, K. H., K. Lee, Y. S. Moon, and H. S. Sul. 2001. A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J. Biol. Chem. 76: 11252-11256
10 Morrison, R. F. and S. R. Farmer. 1999. Insights into the transcriptional control of adipocyte differentiation. J. Cell. Biochem. S32/33: 59-67
11 Ono, Y., E. Hattori, Y. Fukaya, S. Imai, and Y. Ohizumi. 2006. Anti-obesity effect of Nelumbo nucifera leaves extract in mice and rats. J. Ethnopharmacol. 106: 238-244   DOI   ScienceOn
12 Scheja, L., L. Makowski, K. T. Uysal, S. M. Wiesbrock, D. R. Shimshek, D. S. Meyers, M. Morgan, R. A. Parker, and G. S. Hotamisligil. 1999. Altered insulin secretion associated with reduced lipolytic efficiency in a$P2^{-/-}$ mice. Diabetes 48: 1987-1994   DOI   ScienceOn
13 Sumiyoshi, M. and Y. Kimura. 2006. Low molecular weight chitosan inhibits obesity induced by feeding a high-fat diet long-term in mice. J Pharm. Pharmacol. 58: 201-207   DOI   ScienceOn
14 Shin, W. S., J. C. Kil, and G. M. Park. 2006. Antiprotozoal activity of deacetylated chitosan oligosaccharide (dp 2-8) on Trichomonas vaginalis. J. Microbiol. Biotechnol. 16: 1984-1989   과학기술학회마을
15 Si, Y., S. Palani, A. Jayaraman, and K. Lee. 2007. Effects of forced uncoupling protein 1 expression in 3T3-L1 cells on mitochondrial function and lipid metabolism. J. Lipid Res. 48: 826-836   DOI   ScienceOn
16 Spiegelman, B. M. and J. S. Flier. 2001. Obesity and the regulation of energy balance. Cell 104: 531-543   DOI   ScienceOn
17 Tontonoz, P., E. Hu, R. A. Graves, A. I. Budavari, and B. M. Spiegelman. 1994. mPPAR${\gamma}$2: Tissue-specific regulator of an adipocyte enhancer. Genes Develop. 8: 1224-1234   DOI   ScienceOn
18 Wellen, K. E., R. Fucho, M. F. Gregor, M. Furuhashi, C. Morgan, T. Lindstad, E. Vaillancourt, C. Z. Gorgun, F. Saatcioglu, and G. S. Hotamisligil. 2007. Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. Cell 129: 537-548   DOI   ScienceOn
19 Wu, Z., E. D. Rosen, R. Brun, S. Hauser, G. Adelmant, A. E. Troy, C. McKeon, G. J. Darlington, and B. M. Spiegelman. 1999. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Molec. Cell 3: 151-158   DOI   ScienceOn
20 Ntambi, J. M. and K. C. Young. 2000. Adipocyte differentiation and gene expression. J. Nutr. 130: 3122-3126   DOI
21 Juvet, L. K., S. M. Andresen, G. U. Schuster, K. T. Dalen, K. A. Tobin, K. Hollung, F. Haugen, S. Jacinto, S. M. Ulven, K. Bamberg, J. A. Gustafsson, and H. I. Nebb. 2003. On the role of liver X receptors in lipid accumulation in adipocytes. Molec. Endocrinol. 17: 172-182   DOI   ScienceOn
22 Kim, J. B. and B. M. Spiegelman. 1996. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Develop. 10: 1096-1107   DOI   ScienceOn
23 Darlington, G. J., S. E. Ross, and O. A. MacDougald. 1998. The role of C/EBP genes in adipocyte differentiation. J. Biol. Chem. 273: 30057-30060   DOI
24 Gregorie, F. M., C. M. Smas, and H. S. Sul. 1998. Understanding adipocyte differentiation. Physiol. Rev. 78: 783-809   DOI
25 Kahn, B. B. 1998. Type 2 diabetes: When insulin secretion fails to compensate for insulin resistance. Cell 92: 593-596   DOI   ScienceOn
26 Lee, J. H., D. H. Lee, J. H. Son, J. K. Park, and S. K. Kim. 2005. Optimization of chitosan-alginate encapsulation process using pig hepatocytes for development of bioartificial liver. J. Microbiol. Biotechnol. 15: 7-13   과학기술학회마을
27 Cornelius, P., O. A. MacDougald, and M. D. Lane. 1994. Regulation of adipocyte development. Annu. Rev. Nutr. 14: 99-129   DOI   ScienceOn
28 Han, L. K., Y. Kimura, and H. Okuda. 1999. Reduction in fat storage during chitin-chitosan treatment in mice fed a high-fat diet. Int. J. Obesity 23: 174-179   DOI
29 Kim, H. Y., J. R. Kim, and H. S. Kim. 2006. Synergistic effect of interleukin-18 on the expression of lipopolysaccharide-induced IP-10 (CXCL-10) mRNA in mouse peritoneal macrophages. J. Microbiol. Biotechnol. 16: 1605-1612   과학기술학회마을
30 Tabor, D. E., J. B. Kim, B. M. Spiegelman, and P. A. Edwards. 1999. Identification of conserved cis-elements and transcription factors required for sterol-regulated transcription of stearoyl- CoA desaturase 1 and 2. J. Biol. Chem. 274: 20603-20610   DOI
31 Rangwala, S. M. and M. A. Lazar. 2000. Transcriptional control of adipogenesis. Annu. Rev. Nutr. 20: 535-559   DOI   ScienceOn
32 Hwang, C. S., T. M. Loftus, S. Mandrup, and M. D. Lane. 1997. Adipocyte differentiation and leptin expression. Annu. Rev. Cell Develop. Biol. 13: 231-259   DOI   ScienceOn
33 Madsen, L., R. K. Petersen, and K. Kristiansen. 2005. Regulation of adipocyte differentiation and function by polyunsaturated fatty acids. Biochim. Biophys. Acta 1740: 266-286   DOI   ScienceOn
34 Steppan, C. M., S. T. Bailey, S. Bhat, E. J. Brown, R. R. Banerjee, C. M. Wright, H. R. Patel, R. S. Ahima, and M. A. Lazar. 2001. The hormone resistin links obesity to diabetes. Nature 409: 307-312   DOI   ScienceOn
35 MacDougald, O. A. and M. D. Lane. 1995. Transcriptional regulation of gene expression during adipocyte differentiation. Annu. Rev. Biochem. 64: 345-373   DOI   ScienceOn
36 Sharma, A. M. 2002. Adipose tissue: A mediator of cardiovascular risk. Int. J. Obes. Relat. Metab. Disord. S4: S5-S7
37 Ho, S. C., E. S. Tai, P. H. Eng, C. E. Tan, and A. C. Fok. 2001. In the absence of dietary surveillance, chitosan does not reduce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects. Singapore Med. J. 42: 6-10
38 Hu, E., P. Liang, and B. M. Spiegelman. 1996. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 271: 10697-10703   DOI   ScienceOn
39 Fujita, H., H. Fujishima, T. Morii, J. Koshimura, T. Narita, M. Kakei, and S. Ito. 2002. Effect of metformin on adipose tissue resistin expression in db/db mice. Biochem. Biophys. Res. Commun. 298: 345-349   DOI   ScienceOn
40 Gades, M. D. and J. S. Stern. 2003. Chitosan supplementation and fecal fat excretion in men. Obesity Res. 11: 683-688   DOI
41 Kawada, T., N. Takahashi, and T. Fushiki. 2001. Biochemical and physiological characteristics of fat cell. J. Nutr. Sci. Vitaminol. 47: 1-12   DOI   ScienceOn
42 Tontonoz, P., R. A. Graves, A. I. Budavari, H. Erdjument- Bromage, M. Lui, E. Hu, P. Tempst, and B. M. Spiegelman. 1994. Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR${\gamma}$ and RXR. Nucleic Acids Res. 22: 5628-5634   DOI   ScienceOn
43 Trinh, H. T., S. J. Han, S. W. Kim, Y. C. Lee, and D. H. Kim. 2007. Bifidus fermentation increases hypolipidemic and hypoglycemic effects of red ginseng. J. Microbiol. Biotechnol. 17: 1127-1133   과학기술학회마을
44 Furuyashiki, T., H. Nagayasu, Y. Aoki, H. Bessho, T. Hashimoto, K. Kanazawa, and H. Ashida. 2004. Tea catechin suppresses adipocyte differentiation accompanied by downregulation of PPAR$\gamma$2 and C/EBP$\alpha$ in 3T3-L1 cells. Biosci. Biotechnol. Biochem. 68: 2353-2359   DOI   ScienceOn
45 Sfeir, Z., A. Ibrahimi, and E. Amri. 1997. 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 57: 17-21   DOI   ScienceOn
46 Takahashi, N., T. Kawada, T. Yamamoto, T. Goto, A. Taimatsu, N. Aoki, H. Kawasaki, K. Taira, K. K. Yokoyama, Y. Kamei, and T. Fushiki. 2002. Overexpression and ribozyme-mediated targeting of transcriptional coactivators CREB-binding protein and p300 revealed their indispensable roles in adipocyte differentiation through the regulation of peroxisome proliferators activated receptor gamma. J. Biol. Chem. 277: 16906-16912   DOI   ScienceOn
47 Lee, S. J., J. H. Kim, J. H. Kim, M. J. Chung, Q. Wen, H. Chung, K. W. Kim, and Y. S. Yu. 2007. Human apolipoprotein E2 transgenic mice show lipid accumulation in retinal pigment epithelium and altered expression of VEGF and bFGF in the eyes. J. Microbiol. Biotechnol. 17: 1024-1030   과학기술학회마을
48 Rosen, E. D. and B. M. Spiegelman. 2000. Molecular regulation of adipogenesis. Annu. Rev. Cell Develop. Biol. 16: 145-171   DOI   ScienceOn
49 Tontonoz, P., J. B. Kim, R. A. Graves, and B. M. Spiegelman. 1993. ADD1: A novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. Molec. Cell. Biol. 13: 4753-4759   DOI
50 Maeda, K., H. Cao, K. Kono, C. Z. Gorgun, M. Furuhashi, K. T. Uysal, Q. Cao, G. Atsumi, H. Malone, B. Krishnan, Y. Minokoshi, B. B. Kahn, R. A. Parker, and G. S. Hotamisligil. 2005. Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metabol. 1: 107-119   DOI   ScienceOn
51 Havel, P. J. 2000. Role of adipose tissue in body-weight regulation: Mechanisms regulating leptin production and energy balance. Proc. Nutr. Soc. 59: 359-371
52 Fried, S. K. and J. G. Kral. 1986. Sex differences in regional distribution of fat cell size and lipoprotein lipase activity in morbidly obese patients. Int. J. Obesity 11: 129-140
53 Gades, M. D. and J. S. Stern. 2005. Chitosan supplementation and fat absorption in men and women. J. Am. Diet. Assoc. 105: 72-77   DOI   ScienceOn
54 Guerciolini, R., L. Radu-Radulescu, M. Boldrin, J. Dallas, and R. Moore. 2001. Comparative evaluation of fecal fat excretion induced by orlistat and chitosan. Obesity Res. 9: 364-367   DOI
55 Way, J. M., C. Z. Gorgun, Q. Tong, K. T. Uysal, K. K. Brown, W. W. Harrington, W. R. Oliver Jr., T. M. Willson, S. A. Kliewer, and G. S. Hotamisligil. 2001. Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J. Biol. Chem. 276: 25651-25653   DOI   ScienceOn
56 Wu, Z., Y. Xie, N. L. Bucher, and S. R. Farmer. 1995. Conditional ectopic expression of C/EBP$\beta$ in NIH-3T3 cells induces PPAR${\gamma}$ and stimulates adipogenesis. Genes Develop. 9: 2350-2363   DOI   ScienceOn
57 Fujimoto, T., Y. Tsuchiya, M. Terao, K. Nakamura, and M. Yamamoto. 2006. Antibacterial effects of chitosan solution against Legionella pneumophila, Escherichia coli, and Staphylococcus aureus. Int. J. Food Microbiol. 112: 96-101   DOI   ScienceOn
58 Hong, K. H., K. H. Jang, J. C. Lee, S. H. Kim, M. K. Kim, I. Y. Lee, S. M. Kim, Y. H. Lim, and S. A. Kang. 2005. Bacterial $\beta$-glucan exhibits potent hypoglycemic activity via decrease of serum lipids and adiposity, and increase of UCP mRNA expression. J. Microbiol. Biotechnol. 15: 823-830   과학기술학회마을
59 Huang, C., Y. Zhang, Z. Gong, X. Sheng, Z. Li, W. Zhang, and Y. Qin. 2006. Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochem. Biophys. Res. Commun. 348: 571-578   DOI   ScienceOn
60 Coe, N. R., M. A. Simpson, and D. A. Bernlohr. 1999. Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels. J. Lipid Res. 40: 967-972
61 Oberkofler, H., A. Beer, D. Breban, E. Hell, F. Krempler, and W. Patsch. 1997. Human obese gene expression: Alternative splicing of mRNA and relation to adipose tissue localization. Obesity Surg. 7: 390-396   DOI   ScienceOn
62 Scherer, P. E., S. Williams, M. Fogliano, G. Baldini, and H. F. Lodish. 1995. A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. 270: 26746-26749   DOI   ScienceOn
63 Smith, P. J., L. S. Wise, R. Berkowitz, C. Wan, and C. S. Rubin. 1988. Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J. Biol. Chem. 263: 9402-9408
64 Harmon, A. W. and J. B. Harp. 2001. Differential effects of flavonoids on 3T3-L1 adipogenesis and lipolysis. Am. J. Physiol. Cell Physiol. 280: C807-C813   DOI
65 Rosen, E. D., C. J. Walkey, P. Puigserver, and B. M. Spiegelman. 2000. Transcriptional regulation of adipogenesis. Genes Develop. 14: 1293-1307
66 Maffei, M., J. Halaas, E. Ravussin, R. E. Pratley, G. H. Lee, Y. Zhang, H. Fei, S. Kim, R. Lallone, S. Ranganathan, P. A. Kern, and J. M. Friedman. 1995. Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat. Med. 1: 1155-1161   DOI   ScienceOn
67 Fukui, Y. and K. Motojima. 2002. Expression of resistin in the adipose tissue is modulated by various factors including peroxisome proliferator-activated receptor alpha. Diabetes Obesity Metabol. 4: 342-345   DOI   ScienceOn
68 Seo, J. B., H. M. Kim, W. S. Moon, Y. S. Lee, H. W. Jeong, E. J. Yoo, J. Ham, H. Kang, M. G. Park, K. R. Steffensen, T. M. Stulnig, J. A. Gustafsson, S. D. Park, and J. B. Kim. 2004. Activated liver X receptors stimulate adipocyte differentiation through induction of peroxisome proliferatoractivated receptor gamma expression. Molec. Cell. Biol. 24: 3430-3444   DOI   ScienceOn
69 Singla, A. K. and M. Chawla. 2001. Chitosan: Some pharmaceutical and biological aspects - an update. J. Pharm. Pharmacol. 53: 1047-1067   DOI   ScienceOn