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http://dx.doi.org/10.15188/kjopp.2020.06.34.3.136

Roots Extract of Adenophora triphylla var. japonica Inhibits Adipogenesis in 3T3-L1 Cells through the Downregulation of IRS1  

Kim, Hae Lim (NutraPharm Tech Co., Ltd.)
Lee, Hae Jin (NutraPharm Tech Co., Ltd.)
Choi, Bong-Keun (NutraPharm Tech Co., Ltd.)
Park, Sung-Bum (DONG IL Pharmtec Co., Ltd.)
Woo, Sung Min (SM-WOOIL Co., Ltd.)
Lee, Dong-Ryung (NutraPharm Tech Co., Ltd.)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.34, no.3, 2020 , pp. 136-141 More about this Journal
Abstract
The purpose of this study was to investigate the action mechanism of the roots of Adenophora triphylla var. japonica extract (ATE) in 3T3-L1 adipocytes. Cell toxicity test by MTT assay and lipid accumulation was performed to evaluate the inhibitory effect on the differentiation of adipocyte from preadipocytes induced by MDI differentiation medium, while adipogenesis related proteins expression level were evaluated by western blotting. As a result, ATE inhibited MDI-induced adipocyte differentiation in 3T3-L1 cells dose-dependently without cytotoxicity. Our results showed that ATE inhibited the phosphorylation of IRS1, thereby decreasing the expression of PI3K110α and reducing the phosphorylation of AKT and mTOR, resulting in attenuated protein expression of C/EBPα, PPARγ, ap2 and FAS in 3T3-L1 cells. These results suggest anti-adipogenic functions for ATE, and identified IRS1 as a novel target for ATE in adipogenesis.
Keywords
Roots of Adenophora triphylla var. japonica extract; 3T3-L1 Adipocyte; Adipogenesis; Anti-obesity;
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1 Lee IS, Yang EJ, Kim HS, Chung SK, Furukawa F, Nishikawa A. Suppressive effects of Adenophora triphylla extracts on in vitro tumor growth and in vivo gastric epithelial proliferation. Anticancer Res. 2000;20(5A):3227-31.
2 Kim JH, Hong JY, Shin SR, Yoon KY. Comparison of antioxidant activity in wild plant (Adenophora triphylla) leaves and roots as a potential source of functional foods. Int J Food Sci Nutr. 2009;60(Suppl 2):150-61.   DOI
3 Kim AJ, Han MR, Kim MH, Lee MS, Yoon TJ, Ha SD. The antioxidant and chemopreventive potentialities of Mosidae (Adenophora remotiflora) leaves. Nutr Res Pract. 2010;4(1):30-5.   DOI
4 Choi HJ, Chung MJ, Ham SS. Anti-obese and hypocholesterolaemic effects of an Adenophora triphylla extract in HepG2 cells and high fat diet-induced obese mice. Food Chem. 2010;119(2):437-44.   DOI
5 Xing Y, Yan F, Liu Y, Liu Y, Zhao Y. Matrine inhibits 3T3-L1 preadipocyte differentiation associated with suppression of ERK1/2 phosphorylation. Biochemical and biophysical research communications. 2010;396(3):691-5.   DOI
6 Quan X, Wang Y, Ma X, Liang Y, Tian W, Ma Q, Jiang H, Zhao Y. $\alpha$-Mangostin induces apoptosis and suppresses differentiation of 3T3-L1 cells via inhibiting fatty acid synthase. PLoS One. 2012;7(3):e33376.   DOI
7 Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes & development. 2000;14(11):1293-307.
8 Wong RH, Sul HS. Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective. Curr Opin Pharmacol. 2010;10(6):684-91.   DOI
9 Huang KC. The Pharmacology of Chinese Herbs. CRC Press: Boca Raton. 1993.
10 Giri S, Rattan R, Haq E, Khan M, Yasmin R, Won JS, Key L, Singh AK, Singh I. AICAR inhibit adipocyte differentiation in 3T3L1 and restores metabolic alteractions in diet-induced obesity mice model. Nutr Metab. 2006;3(1):31-50.   DOI
11 Kim SK, Kong CS. Anti-adipogenic effect of dioxinodehydoeckol via AMPK activation in 3T3-L1 adipocytes. Chem Biol. 2010;186(1):24-9.
12 Sesti G, Federici M, Hribal ML, Lauro D, Sbraccia P, Lauro R. Defects of the insulin recptor substrate (IRS) system in human metabolic disorders. J FASEB. 2001;15(12):2099-111.   DOI
13 Kopelman PG. Obesity as a medical problem. Nature. 2000;404(6778):635-43.   DOI
14 Kang SI, Shin HS, Kim SJ. Sinensetin enhances adipogenesis and lipolysis by increasing cyclic adenosine monophosphate levels in 3T3-L1 adipocytes. Biol Pharm Bull. 2015;38(4):552-8.   DOI
15 Park JY, Kim Y, Im J, You S, Lee H. Inhibition of adipogenesis by oligonol through Akt-mTOR inhibition in 3T3-L1 adipocytes. Evidence-Based Complementary and Alternative Medicine. 2014;2014.
16 Khan A, Pessin J. Insulin regulation of glucose uptake: a complex interplay of intracellular signaling pathways. Diabetologia. 2002;45(11):1475-83.   DOI
17 Magun R, Burgering BM, Coffer PJ, Pardasani D, Lin Y, Chabot J, Sorisky A. Expression of a constitutively activated form of protein kinase B (c-Akt) in 3T3-L1 preadipose cells causes spontaneous differentiation. Endocrinology. 1996;137(8):3590-3.   DOI
18 Xu J, Liao K. Protein kinase B/AKT1 plays a pivotal role in insulin-like growth factor-1 receptor signaling induced 3T3-L1 adipocyte differentiation. J Biol Chem. 2004;279(34):35914-22.   DOI
19 Adochio R, Leitner JW, Hedlund R, Draznin B. Rescuing 3T3-L1 adipocytes from insulin resistance induced by stimulation of Akt-mammalian target of rapamycin/p70 S6 Kinase (S6K1). Pathway and serine phosphorylation of insulin receptor substrate-1: effect of reduced expression of $p85{\alpha}$ subunit of phosphatidylinositol 3-kinase and S6K1 kinase. Endocrinology. 2008;150(3):1165-73.   DOI
20 Prusty D, Park BH, Davis KE, Farmer SR. Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor $\gamma$ ($PPAR{\gamma}$) and $C/EBP{\alpha}$ gene expression during the differentiation of 3T3-L1 preadipocytes. Journal of Biological Chemistry. 2002;277(48):46226-32.   DOI
21 Lee DR, Lee YS, Choi BK, Lee HJ, Park SB, Kim TM, Oh HJ, Yang SH, Suh JW. Roots extracts of Adenophora triphylla var. japonica improve obesity in 3T3-L1 adipocytes and high-fat diet-induced obese mice. Asian Pacific journal of tropical medicine. 2015;8(11):898-906.   DOI
22 Gan L, Liu Z, Jin W, Zhou Z, Sun C. Foxc2 enhances proliferation and inhibits apoptosis through activating Akt/mTORC1 signaling pathway in mouse preadipocytes. Journal of lipid research. 2015;56(8):1471-80.   DOI
23 Kim JE, Chen J. Regulation of peroxisome proliferator-activated receptor-$\gamma$ activity by mammalian target of rapamycin and amino acids in adipogenesis. Diabetes. 2004;53(11): 2748-56.   DOI
24 Konno C, Saito T, Oshima Y, Hikino H, Kabuto C. Structure of methyl adenophorate and triphyllol, triterpenoids of Adenophora triphylla var. japonica roots. Planta Med. 1981;42(7):268-74.   DOI
25 Araki E, Lipes MA, Patti ME, Bruning JC, Haag III B, Johnson RS, Kahn CR. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature. 1994;372(6502):186.   DOI
26 Aubert J, Dessolin S, Belmonte N, Li M, McKenzie FR, Staccini L, Villageois P, Barhanin B, Vernallis A, Smith A G, Ailhaud G, Dani C. Leukemia inhibitory factor and its receptor promote adipocyte differentiation via the mitogen-activated protein kinase cascade. Journal of Biological Chemistry. 1999;274(35):24965-72.   DOI
27 White MF. IRS proteins and the common path to diabetes. American Journal of Physiology-Endocrinology And Metabolism. 2002;283(3):E413-E422.   DOI
28 SESTI G, FEDERICI M, HRIBAL ML, LAURO D, SBRACCIA P, LAURO R. Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. The FASEB Journal. 2001;15(12):2099-111.   DOI
29 Tamemoto H, Kadowaki T, Tobe K, Yagi T, Sakura H, Hayakawa T, Terauchi Y, Ueki K, Kaburagi Y, Satoh S, Sekihara H, Yoshioka S, Horikoshi H, Furuta Y, Ikawa Y, Kasuga M, Yazaki Y, Sekihara, H. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature.1994;372(6502):182.   DOI
30 Bruning JC, Winnay J, Cheatham B, Kahn CR. Differential signaling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1-deficient cells. Molecular and cellular biology. 1997;17(3):1513-21.   DOI