Roots Extract of Adenophora triphylla var. japonica Inhibits Adipogenesis in 3T3-L1 Cells through the Downregulation of IRS1
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (30)
- Giri S, "AICAR inhibit adipocyte differentiation in 3T3L1 and restores metabolic alteractions in diet-induced obesity mice model", Nutr Metab, 3(1), pp.31~50 (2006)
- Kim SK, "Anti-adipogenic effect of dioxinodehydoeckol via AMPK activation in 3T3-L1 adipocytes", Chem Biol, 186(1), pp.24~29 (2010)
- Kopelman PG, "Obesity as a medical problem", Nature, 404(6778), pp.635~643 (2000)
- Kang SI, "Sinensetin enhances adipogenesis and lipolysis by increasing cyclic adenosine monophosphate levels in 3T3-L1 adipocytes", Biol Pharm Bull, 38(4), pp.552~558 (2015)
- Park JY, "Inhibition of adipogenesis by oligonol through Akt-mTOR inhibition in 3T3-L1 adipocytes", Evidence-Based Complementary and Alternative Medicine, 2014 (2014)
- Sesti G, "Defects of the insulin recptor substrate(IRS)system in human metabolic disorders", J FASEB, 15(12), pp.2099~2111 (2001)
- Khan A, "Insulin regulation of glucose uptake : a complex interplay of intracellular signaling pathways", Diabetologia, 45(11), pp.1475~1483 (2002)
- Magun R, "Expression of a constitutively activated form of protein kinase B(c-Akt)in 3T3-L1 preadipose cells causes spontaneous differentiation", Endocrinology, 137(8), pp.3590~3593 (1996)
- Xu J, "Protein kinase B", AKT1 plays a pivotal role in insulin-like growth factor-1 receptor signaling induced 3T3-L1 adipocyte differentiation, 2004, pp.279(34), 35914~35922
- Adochio R, "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 p85α subunit of phosphatidylinositol 3-kinase and S6K1 kinase, 2008, pp.150(3), 1165~1173
- Gan L, "Foxc2 enhances proliferation and inhibits apoptosis through activating Akt", mTORC1 signaling pathway in mouse preadipocytes, 2015, pp.56(8), 1471~1480
- Kim JE, "Regulation of peroxisome proliferator–activated receptor-γ activity by mammalian target of rapamycin and amino acids in adipogenesis", Diabetes, 53(11), pp.2748~2756 (2004)
- Konno C, "Structure of methyl adenophorate and triphyllol, triterpenoids of Adenophora triphylla var. japonica roots", Planta Med, 42(7), pp.268~274 (1981)
- Lee DR, "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, 8(11), pp.898~906 (2015)
- Huang KC, "The Pharmacology of Chinese Herbs" (1993), CRC Press
- Lee IS, "Suppressive effects of Adenophora triphylla extracts on in vitro tumor growth and in vivo gastric epithelial proliferation", Anticancer Res, 20(5A), pp.3227~3231 (2000)
- Kim JH, "Comparison of antioxidant activity in wild plant(Adenophora triphylla)leaves and roots as a potential source of functional foods", Int J Food Sci Nutr, 60(Suppl 2), pp.150~161 (2009)
- 김애정, "The antioxidant and chemopreventive potentialities of Mosidae (Adenophora remotiflora) leaves", Nutrition Research and Practice, 4(1), pp.30~35 (2010), 한국영양학회
- Choi HJ, "Anti-obese and hypocholesterolaemic effects of an Adenophora triphylla extract in HepG2 cells and high fat diet-induced obese mice", Food Chem, 119(2), pp.437~444 (2010)
- Xing Y, "Matrine inhibits 3T3-L1 preadipocyte differentiation associated with suppression of ERK1", 2 phosphorylation, 2010, pp.396(3), 691~695
- Quan X, "α-Mangostin induces apoptosis and suppresses differentiation of 3T3-L1 cells via inhibiting fatty acid synthase", PLoS One, 7(3), pp.e33376~ (2012)
- Rosen ED, "Transcriptional regulation of adipogenesis", Genes & development, 14(11), pp.1293~1307 (2000)
- Wong RH, "Insulin signaling in fatty acid and fat synthesis : a transcriptional perspective", Curr Opin Pharmacol, 10(6), pp.684~691 (2010)
- Prusty D, "Activation of MEK", ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor γ(PPARγ)and C, Journal of Biological Chemistry, pp.2002, 277(48)[DOI]
- Aubert J, "Leukemia inhibitory factor and its receptor promote adipocyte differentiation via the mitogen-activated protein kinase cascade", Journal of Biological Chemistry, 274(35), pp.24965~24972 (1999)
- White MF, "IRS proteins and the common path to diabetes", American Journal of Physiology-Endocrinology And Metabolism, 283(3), pp.E413~E422 (2002)
- SESTI G, "Defects of the insulin receptor substrate(IRS)system in human metabolic disorders", The FASEB Journal, 15(12), pp.2099~2111 (2001)
- Araki E, "Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene", Nature, 372(6502), pp.186~ (1994)
- Tamemoto H, "Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1", Nature, 372(6502), pp.182~ (1994)
- Brüning JC, "Differential signaling by insulin receptor substrate 1(IRS-1)and IRS-2 in IRS-1-deficient cells", Molecular and cellular biology, 17(3), pp.1513~1521 (1997)