Altered Gelidium elegans Extract-stimulated Beige-like Phenotype Attenuates Adipogenesis in 3T3-L1 Cells

Jia Choi¹, Kui-Jin Kim¹, Eun-Jeong Koh¹ and Boo-Yong Lee^1,

¹Department of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyeonggi 463-400, Republic of Korea

Cite this paper:
Jia Choi, Kui-Jin Kim, Eun-Jeong Koh and Boo-Yong Lee. Altered Gelidium elegans Extract-stimulated Beige-like Phenotype Attenuates Adipogenesis in 3T3-L1 Cells. Journal of Food and Nutrition Research. 2016; 4(7):448-453. doi: 10.12691/jfnr-4-7-6

Abstract

Previously, we showed that Gelidium elegans extract (GE) suppresses oxidative stress and lipid accumulation. However, the molecular mechanism underlying the anti-adipogenic ability of GE is still unclear. The levels of adipogenesis markers and triglyceride synthesis enzymes were measured by western blot. To evaluate the lipid accumulation in 3T3-L1 cells, oil red o staining was performed. We investigated whether GE induces lipolysis by measuring adipocyte triglyceride lipase (ATGL) during adipocyte differentiation. We also examined the expression of beige cell-associated genes and the production of carbon dioxide in 3T3-L1 cells. We showed that GE increased the protein expression of CAAT/enhancer binding protein (C/EBP) homologous protein 10 and inhibited the expression of C/EBPβ. GE discouraged triglyceride synthesis via deregulation of lysophosphatidic acid acyltransferase-θ (LPAATθ) and diacylglycerolacyltransferase 1 (DGAT1) during late-stage adipogenesis in 3T3-L1 cells. GE also dramatically increased ATGL in 3T3-L1 cells. Finally, in 3T3-L1 cells treated with GE, markers of beige adipocytes such as PRDM16 and UCP1 were upregulated, and large amounts of carbon dioxide were produced. These data indicate that GE suppresses adipogenesis by stimulating a beige-like phenotype in 3T3-L1 cells.

Keywords:
gelidium elegans hesperidin obesity transdifferentiation brown adipocyte energy expenditure

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Asano, H., Kanamori, Y., Higurashi, S., Nara, T., Kato, K., Matsui, T., & Funaba, M. (2014). Induction of beige-like adipocytes in 3T3-L1 cells. J Vet Med Sci, 76(1), 57-64.
[2]	Bilan, M. I., Grachev, A. A., Ustuzhanina, N. E., Shashkov, A. S., Nifantiev, N. E., & Usov, A. I. (2002). Structure of a fucoidan from the brown seaweed Fucus evanescens C.Ag. Carbohydr Res, 337(8), 719-730.
[3]	Cannon, B., & Nedergaard, J. (2004). Brown adipose tissue: function and physiological significance. Physiol Rev, 84(1), 277-359.
[4]	Chizhov, A. O., Dell, A., Morris, H. R., Haslam, S. M., McDowell, R. A., Shashkov, A. S., . . . Usov, A. I. (1999). A study of fucoidan from the brown seaweed Chorda filum. Carbohydr Res, 320(1-2), 108-119.
[5]	Collins, S., & Surwit, R. S. (2001). The beta-adrenergic receptors and the control of adipose tissue metabolism and thermogenesis. Recent Prog Horm Res, 56, 309-328.
[6]	Cornelius, P., MacDougald, O. A., & Lane, M. D. (1994). Regulation of adipocyte development. Annu Rev Nutr, 14, 99-129.
[7]	Darlington, G. J., Ross, S. E., & MacDougald, O. A. (1998). The role of C/EBP genes in adipocyte differentiation. J Biol Chem, 273(46), 30057-30060.
[8]	Dubois, M., Gilles, K., Hamilton, J. K., Rebers, P. A., & Smith, F. (1951). A colorimetric method for the determination of sugars. Nature, 168(4265), 167.
[9]	Grundy, S. M. (2004). Obesity, metabolic syndrome, and cardiovascular disease. The Journal of Clinical Endocrinology & Metabolism, 89(6), 2595-2600.
[10]	Guilherme, A., Virbasius, J. V., Puri, V., & Czech, M. P. (2008). Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol, 9(5), 367-377.
[11]	Jeon, H.-J., Choi, H.-S., Lee, O.-H., Jeon, Y.-J., & Lee, B.-Y. (2012). Inhibition of Reactive Oxygen Species (ROS) and Nitric Oxide (NO) by Gelidium elegans Using Alternative Drying and Extraction Conditions in 3T3-L1 and RAW 264.7 Cells. Preventive nutrition and food science, 17(2), 122.
[12]	Jeon, H. J., Seo, M. J., Choi, H. S., Lee, O. H., & Lee, B. Y. (2014). Gelidium elegans, an Edible Red Seaweed, and Hesperidin Inhibit Lipid Accumulation and Production of Reactive Oxygen Species and Reactive Nitrogen Species in 3T3‐L1 and RAW264. 7 Cells. Phytotherapy Research, 28(11), 1701-1709.
[13]	Kajimura, S., & Saito, M. (2014). A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis. Annu Rev Physiol, 76, 225-249.
[14]	Kelley, D. E., & Goodpaster, B. H. (2001). Skeletal muscle triglyceride an aspect of regional adiposity and insulin resistance. Diabetes Care, 24(5), 933-941.
[15]	Kim, K.-J., & Lee, B.-Y. (2012). Fucoidan from the sporophyll of Undaria pinnatifida suppresses adipocyte differentiation by inhibition of inflammation-related cytokines in 3T3-L1 cells. Nutrition Research, 32(6), 439-447.
[16]	Kim, K.-J., Yoon, K.-Y., & Lee, B.-Y. (2012). Low molecular weight fucoidan from the sporophyll of Undaria pinnatifida suppresses inflammation by promoting the inhibition of mitogen-activated protein kinases and oxidative stress in RAW264.7 cells. Fitoterapia, 83(8), 1628-1635.
[17]	Klaus, S., Ely, M., Encke, D., & Heldmaier, G. (1995). Functional assessment of white and brown adipocyte development and energy metabolism in cell culture. Dissociation of terminal differentiation and thermogenesis in brown adipocytes. J Cell Sci, 108 ( Pt 10), 3171-3180.
[18]	Koh, E.-J., Kim, K.-J., Choi, J., Jeon, H. J., Seo, M.-J., & Lee, B.-Y. Ginsenoside Rg1 suppresses early stage of adipocyte development via activation of C/EBP homologous protein-10 in 3T3-L1 and attenuates fat accumulation in high fat diet-induced obese zebrafish. Journal of Ginseng Research.
[19]	Lee, O.-H., Yoon, K.-Y., Kim, K.-J., You, S., & Lee, B.-Y. (2011). SEAWEED EXTRACTS AS A POTENTIAL TOOL FOR THE ATTENUATION OF OXIDATIVE DAMAGE IN OBESITY-RELATED PATHOLOGIES1. Journal of Phycology, 47(3), 548-556.
[20]	Lowe, C. E., O'Rahilly, S., & Rochford, J. J. (2011). Adipogenesis at a glance. J Cell Sci, 124(Pt 16), 2681-2686.
[21]	Lowell, B. B., & Spiegelman, B. M. (2000). Towards a molecular understanding of adaptive thermogenesis. Nature, 404(6778), 652-660.
[22]	Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J Biol Chem, 193(1), 265-275.
[23]	Martino, H. S. D., Dias, M. M. d. S., Noratto, G., Talcott, S., & Mertens-Talcott, S. U. (2016). Anti-lipidaemic and anti-inflammatory effect of açai (Euterpe oleracea Martius) polyphenols on 3T3-L1 adipocytes. Journal of Functional Foods, 23, 432-443.
[24]	Miller, C. N., Yang, J. Y., England, E., Yin, A., Baile, C. A., & Rayalam, S. (2015). Isoproterenol Increases Uncoupling, Glycolysis, and Markers of Beiging in Mature 3T3-L1 Adipocytes. PLoS One, 10(9), e0138344.
[25]	Nadra, K., Medard, J. J., Mul, J. D., Han, G. S., Gres, S., Pende, M., . . . Chrast, R. (2012). Cell autonomous lipin 1 function is essential for development and maintenance of white and brown adipose tissue. Mol Cell Biol, 32(23), 4794-4810.
[26]	Phan, J., & Reue, K. (2005). Lipin, a lipodystrophy and obesity gene. Cell Metab, 1(1), 73-83. doi:10.1016/j.cmet.2004.12.002
[27]	Poulos, S. P., Dodson, M. V., & Hausman, G. J. (2010). Cell line models for differentiation: preadipocytes and adipocytes. Exp Biol Med (Maywood), 235(10), 1185-1193.
[28]	Rosen, E. D., Walkey, C. J., Puigserver, P., & Spiegelman, B. M. (2000). Transcriptional regulation of adipogenesis. Genes & development, 14(11), 1293-1307.
[29]	Ryu, S.-J., Choi, H.-S., Yoon, K.-Y., Lee, O.-H., Kim, K.-J., & Lee, B.-Y. (2015). Oleuropein Suppresses LPS-Induced Inflammatory Responses in RAW 264.7 Cell and Zebrafish. J Agric Food Chem, 63(7), 2098-2105.
[30]	Seale, P., Kajimura, S., Yang, W., Chin, S., Rohas, L. M., Uldry, M., . . . Spiegelman, B. M. (2007). Transcriptional control of brown fat determination by PRDM16. Cell Metab, 6(1), 38-54.
[31]	Shi, Y., & Cheng, D. (2009). Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism. American Journal of Physiology - Endocrinology and Metabolism, 297(1), E10-E18.
[32]	Wahba, I. M., & Mak, R. H. (2007). Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol, 2(3), 550-562.
[33]	Yoshie-Stark, Y., Hsieh, Y.-P., & Suzuki, T. (2003). Distribution of flavonoids and related compounds from seaweeds in Japan. Journal-Tokyo University of Fisheries, 89, 1-6.
[34]	Zhang, P., O'Loughlin, L., Brindley, D. N., & Reue, K. (2008). Regulation of lipin-1 gene expression by glucocorticoids during adipogenesis. Journal of lipid research, 49(7), 1519-1528.