Acer okamotoanum Nakai Leaf Extract Inhibits Adipogenesis Via Suppressing Expression of PPAR γ and C/EBP α in 3T3-L1 Cells
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초록
The genus Acer contains several species with various bioactivities including antioxidant, antitumor and anti-inflammatory properties. However, Acer okamotoanum Nakai, one species within this genus has not been fully studied yet. Therefore, in this study, we investigated the anti-adipogenic activities of leaf extract from A. okamotoanum Nakai (LEAO) on 3T3-L1 preadipocytes. Adipogenesis is one of the cell differentiation processes, which converts preadipocytes into mature adipocytes. Nowadays, inhibition of adipogenesis is considered as an effective strategy in the field of anti-obesity research. In this study, we observed that LEAO decreased the accumulation of lipid droplets during adipogenesis and down-regulated the expression of key adipogenic transcription factors such as peroxisome proliferator-activated receptor γ (PPAR γ) and CCAAT/enhancer binding protein α (C/EBP α). In addition, LEAO inactivated PI3K/Akt signaling and its downstream factors that promote adipogenesis by inducing the expression of PPAR γ. LEAO also activated β-catenin signaling, which prevents the adipogenic program by suppressing the expression of PPAR γ. Therefore, we found that treatment with LEAO is effective for attenuating adipogenesis in 3T3-L1 cells. Consequently, these findings suggest that LEAO has the potential to be used as a therapeutic agent for preventing obesity.
Abstract
The genus Acer contains several species with various bioactivities including antioxidant, antitumor and anti-inflammatory properties. However, Acer okamotoanum Nakai, one species within this genus has not been fully studied yet. Therefore, in this study, we investigated the anti-adipogenic activities of leaf extract from A. okamotoanum Nakai (LEAO) on 3T3-L1 preadipocytes. Adipogenesis is one of the cell differentiation processes, which converts preadipocytes into mature adipocytes. Nowadays, inhibition of adipogenesis is considered as an effective strategy in the field of anti-obesity research. In this study, we observed that LEAO decreased the accumulation of lipid droplets during adipogenesis and down-regulated the expression of key adipogenic transcription factors such as peroxisome proliferator-activated receptor γ (PPAR γ) and CCAAT/enhancer binding protein α (C/EBP α). In addition, LEAO inactivated PI3K/Akt signaling and its downstream factors that promote adipogenesis by inducing the expression of PPAR γ. LEAO also activated β-catenin signaling, which prevents the adipogenic program by suppressing the expression of PPAR γ. Therefore, we found that treatment with LEAO is effective for attenuating adipogenesis in 3T3-L1 cells. Consequently, these findings suggest that LEAO has the potential to be used as a therapeutic agent for preventing obesity.
참고문헌 (37)
- Pi-Sunyer FX., "The obesity epidemic: pathophysiology and consequences of obesity", Obesity, 10, pp.97S~104S (2002)
- Lawrence VJ, "Medical consequences of obesity", Clin. Dermatol, 22, pp.296~302 (2004)
- Marti A, "Genes, lifestyles and obesity", Int. J. Obes, 28, pp.S29~S36 (2004)
- Spiegelman BM, "Adipogenesis and obesity:rounding out the big picture", Cell, 87, pp.377~389 (1996)
- Ali AT, "Adipocyte and adipogenesis", Eur. J. Cell Biol, 92, pp.229~236 (2013)
- Farmer SR., "Transcriptional control of adipocyte formation", Cell Metabolism, 4, pp.263~273 (2006)
- Rosen ED, "Adipocyte differentiation from the inside out. Nature Reviews", Mol. Cell Biol, 7, pp.885~896 (2006)
- Rosen ED, "PPAR γ is required for the differentiation of adipose tissue in vivo and in vitro", Mol. Cell, 4, pp.611~617 (1999)
- Saltiel AR, "Insulin signalling and the regulation of glucose and lipid metabolism", Nature, 414, pp.799~806 (2001)
- Laplante M, "mTOR signaling in growth control and disease", Cell, 149, pp.274~293 (2012)
- Christodoulides C, "Adipogenesis and WNT signalling", Trends Endocrinol. Metab, 20, pp.16~24 (2009)
- Bi W, "Traditional uses, phytochemistry, and pharmacology of the genus Acer (maple): a review", J. Ethnopharmacol, 189, pp.31~60 (2016)
- 김영, "고로쇠와 우산고로쇠 나무의 항산화능 및 glutathione S-transferase 활성 비교", 한국약용작물학회지, 16(6), pp.427~433 (2008), 한국약용작물학회
- Yang H, "Beneficial effects of Acer okamotoanum sap on L-NAMEinduced hypertension-like symptoms in a rat model", Mol. Med. Rep, 5, pp.427~431 (2012)
- Yoo Y, "The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats", Int. J. Mol. Med, 28, pp.489~495 (2011)
- Rayalam S, "Phytochemicals and regulation of the adipocyte life cycle", J. Nutr. Biochem, 19, pp.717~726 (2008)
- Yun JW, "Possible anti-obesity therapeutics from nature–a review", Phytochemistry, 71, pp.1625~1641 (2010)
- Feng S, "Potential of natural products in the inhibition of adipogenesis through regulation of PPAR γ expression and", or its transcriptional activity, 2016, pp.21, 1278~
- activity during adipogenesis, "Int. J. Obes", 2005, S13~S16
- Rosen ED, "C", EBPalpha induces adipogenesis through PPARgamma: a unified pathway, 2002, pp.16, 22~26
- Eberlé D, "SREBP transcription factors : master regulators of lipid homeostasis", Biochimie, 86, pp.839~848 (2004)
- Kim JB, "ADD1", SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism, 1996, pp.10, 1096~1107
- Chirala SS, "Structure and function of animal fatty acid synthase", Lipids, 39, pp.1045~1053 (2004)
- Fu Y, "Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation", J. Lipid Res, 46, pp.1369~1379 (2005)
- Whitehead JP, "Signalling through the insulin receptor", Curr. Opin. Cell Biol, 12, pp.222~228 (2000)
- Khan A, "Insulin regulation of glucose uptake : a complex interplay of intracellular signalling pathways", Diabetologia, 45, pp.1475~1483 (2002)
- Sasaki T, "Mammalian phosphoinositide kinases and phosphatases", Prog. Lipid Res, 48, pp.307~343 (2009)
- Zhang HH, "Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway", PLoS One, 4, pp.e6189~ (2009)
- Kim JE, "Regulation of peroxisome proliferatoractivated receptor-gamma activity by mammalian target of rapamycin and amino acids in adipogenesis", Diabetes, 53, pp.2748~2756 (2004)
- Laplante M, "An emerging role of mTOR in lipid biosynthesis", Curr. Biol, 19, pp.R1046~R1052 (2009)
- Fox HL, "Amino acids stimulate phosphorylation of p70S6k and organization of rat adipocytes into multicellular clusters", Am. J. Physiol, 274, pp.C206~C213 (1998)
- Wu D, "GSK3: a multifaceted kinase in Wnt signaling", Trends Biochem. Sci, 35, pp.161~168 (2010)
- Taurin S, "Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase", J. Biol. Chem, 281, pp.9971~9976 (2006)
- Grimes CA, "The multifaceted roles of glycogen synthase kinase 3β in cellular signaling", Prog. Neurobiol, 65, pp.391~426 (2001)
- Ding VW, "Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling", J. Biol. Chem, 275, pp.32475~32481 (2000)
- Fang D, "Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity", J. Biol. Chem, 282, pp.11221~11229 (2007)
- Liu J, "Regulating the balance between peroxisome proliferator-activated receptor gamma and betacatenin signaling during adipogenesis. A glycogen synthase kinase 3beta phosphorylation-defective mutant of betacatenin inhibits expression of a subset of adipogenic genes", J. Biol. Chem, 279, pp.45020~45027 (2004)