Arctiin inhibits adipogenesis in 3T3-L1 cells and decreases adiposity and body weight in mice fed a high-fat diet
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BACKGROUND/OBJECTIVES: The purpose of this study was to examine the effects and associated mechanisms of arctiin, alignan compound found in burdock, on adipogenesis in 3T3-L1 cells. Also, the effects of arctiin supplementation in obesemice fed a high-fat diet on adiposity were examined. MATERIALS/METHODS: 3T3-L1 cells were treated with arctiin (12.5 to 100 μM) during differentiation for 8 days. The accumulationof lipid droplets was determined by Oil Red O staining and intracellular triglyceride contents. The expressions of genes relatedto adipogenesis were measured by real-time RT-PCR and Western blot analyses. For in vivo study, C57BL/6J mice were firstfed either a control diet (CON) or high-fat diet (HF) to induce obesity, and then fed CON, HF, or HF with 500 mg/kg BW arctiin(HF + AC) for four weeks. RESULTS: Arctiin treatment to 3T3-L1 pre-adipocytes markedly decreased adipogenesis in a dose-dependent manner. The arctiintreatment significantly decreased the protein levels of the key adipogenic regulators PPARγ and C/EBPα, and also significantlyinhibited the expression of SREBP-1c, fatty acid synthase, fatty acid-binding protein and lipoprotein lipase. Also, arctiin greatlyincreased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoAcarboxylase. Furthermore, administration of arctiin significantly decreased the body weight in obese mice fed with the high-fatdiet. The epididymal, perirenal or total visceral adipose tissue weights of mice were all significantly lower in the HF + AC thanin the HF. Arctiin administration also decreased the sizes of lipid droplets in the epididymal adipose tissue. CONCLUSIONS: Arctiin inhibited adipogenesis in 3T3-L1 adipocytes through the inhibition of PPARγ and C/EBPα and the activationof AMPK signaling pathways. These findings suggest that arctiin has a potential benefit in preventing obesity.
Abstract
BACKGROUND/OBJECTIVES: The purpose of this study was to examine the effects and associated mechanisms of arctiin, alignan compound found in burdock, on adipogenesis in 3T3-L1 cells. Also, the effects of arctiin supplementation in obesemice fed a high-fat diet on adiposity were examined. MATERIALS/METHODS: 3T3-L1 cells were treated with arctiin (12.5 to 100 μM) during differentiation for 8 days. The accumulationof lipid droplets was determined by Oil Red O staining and intracellular triglyceride contents. The expressions of genes relatedto adipogenesis were measured by real-time RT-PCR and Western blot analyses. For in vivo study, C57BL/6J mice were firstfed either a control diet (CON) or high-fat diet (HF) to induce obesity, and then fed CON, HF, or HF with 500 mg/kg BW arctiin(HF + AC) for four weeks. RESULTS: Arctiin treatment to 3T3-L1 pre-adipocytes markedly decreased adipogenesis in a dose-dependent manner. The arctiintreatment significantly decreased the protein levels of the key adipogenic regulators PPARγ and C/EBPα, and also significantlyinhibited the expression of SREBP-1c, fatty acid synthase, fatty acid-binding protein and lipoprotein lipase. Also, arctiin greatlyincreased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoAcarboxylase. Furthermore, administration of arctiin significantly decreased the body weight in obese mice fed with the high-fatdiet. The epididymal, perirenal or total visceral adipose tissue weights of mice were all significantly lower in the HF + AC thanin the HF. Arctiin administration also decreased the sizes of lipid droplets in the epididymal adipose tissue. CONCLUSIONS: Arctiin inhibited adipogenesis in 3T3-L1 adipocytes through the inhibition of PPARγ and C/EBPα and the activationof AMPK signaling pathways. These findings suggest that arctiin has a potential benefit in preventing obesity.
참고문헌 (35)
- "Obesity and overweight" (2014)[URL]
- Konige M, "Role of adipose specific lipid droplet proteins in maintaining whole body energy homeostasis", Biochim Biophys Acta, 1842, pp.393~401 (2014)
- Després JP, "Abdominal obesity and metabolic syndrome", Nature, 444, pp.881~887 (2006)
- Kopelman PG, "Obesity as a medical problem", Nature, 404, pp.635~643 (2000)
- Grundy SM, "Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute", American Heart Association conference on scientific issues related to definition, 2004, pp.109, 433~438
- Kahn BB, "Obesity and insulin resistance", J Clin Invest, 106, pp.473~481 (2000)
- Siersbaek R, "PPARgamma in adipocyte differentiation and metabolism--novel insights from genome-wide studies", FEBS Lett, 584, pp.3242~3249 (2010)
- Bastie C, "Expression of peroxisome proliferator-activated receptor PPARdelta promotes induction of PPARgamma and adipocyte differentiation in 3T3C2 fibroblasts", J Biol Chem, 274, pp.21920~21925 (1999)
- He W, "Adipose-specific peroxisome proliferatoractivated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle", Proc Natl Acad Sci U S A, 100, pp.15712~15717 (2003)
- Wang ND, "Impaired energy homeostasis in C", EBP alpha knockout mice, 1995, pp.269, 1108~1112
- Lin FT, "CCAAT", enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program, 1994, pp.91, 8757~8761
- Wu Z, "Cross-regulation of C", EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity, 1999, pp.3, 151~158
- Farmer SR, "Regulation of PPARgamma activity during adipogenesis", Int J Obes (Lond), 29(Suppl 1), pp.S13~S16 (2005)
- White UA, "Transcriptional factors that promote formation of white adipose tissue", Mol Cell Endocrinol, 318, pp.10~14 (2010)
- Bae CR, "Quercetin-rich onion peel extract suppresses adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 adipocytes", J Sci Food Agric (2014)
- Hayashi K, "Therapeutic effect of arctiin and arctigenin in immunocompetent and immunocompromised mice infected with influenza A virus", Biol Pharm Bull, 33, pp.1199~1205 (2010)
- Matsuzaki Y, "Arctiin induces cell growth inhibition through the down-regulation of cyclin D1 expression", Oncol Rep, 19, pp.721~727 (2008)
- Wu JG, "Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats", Phytomedicine, 16, pp.1033~1041 (2009)
- Lee S, "Anti-inflammatory function of arctiin by inhibiting COX-2 expression via NF-kappaB pathways", J Inflamm (Lond), 8, pp.16~ (2011)
- Tice A, "Access to care: the physician's perspective", Hawaii Med J, 70, pp.33~38 (2011)
- 김우경, "Peanut sprout ethanol extract inhibits the adipocyte proliferation, differentiation, and matrix metalloproteinases activities in mouse fibroblast 3T3-L1 preadipocytes", Nutrition Research and Practice, 7(3), pp.160~165 (2013), 한국영양학회
- Masayuki Yamasaki, "Anti-obesity effects of hot water extract from Wasabi (Wasabia japonica Matsum.) leaves in mice fed high-fat diets", Nutrition Research and Practice, 7(4), pp.267~272 (2013), 한국영양학회
- Yao X, "Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway", J Cell Biochem, 112, pp.2837~2849 (2011)
- Awale S, "Identification of arctigenin as an antitumor agent having the ability to eliminate the tolerance of cancer cells to nutrient starvation", Cancer Res, 66, pp.1751~1757 (2006)
- Ntambi JM, "Adipocyte differentiation and gene expression", J Nutr, 130, pp.3122S~3126S (2000)
- Ali AT, "Adipocyte and adipogenesis", Eur J Cell Biol, 92, pp.229~236 (2013)
- Wang S, "Novel insights of dietary polyphenols and obesity", J Nutr Biochem, 25, pp.1~18 (2014)
- Kim JB, "ADD1", SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism, 1996, pp.10, 1096~1107
- Kim JB, "ADD1", SREBP1 activates PPARgamma through the production of endogenous ligand, 1998, pp.95, 4333~4337
- Ceddia RB, "The role of AMP-activated protein kinase in regulating white adipose tissue metabolism", Mol Cell Endocrinol, 366, pp.194~203 (2013)
- Daval M, "Functions of AMP-activated protein kinase in adipose tissue", J Physiol, 574, pp.55~62 (2006)
- Habinowski SA, "The effects of AICAR on adipocyte differentiation of 3T3-L1 cells", Biochem Biophys Res Commun, 286, pp.852~856 (2001)
- Lee H, "AICAR, an activator of AMPK, inhibits adipogenesis via the WNT", beta-catenin pathway in 3T3-L1 adipocytes, 2011, pp.28, 65~71
- Vingtdeux V, "Small-molecule activators of AMP-activated protein kinase (AMPK), RSVA314 and RSVA405, inhibit adipogenesis", Mol Med, 17, pp.1022~1030 (2011)
- Kuo DH, "Body weight management effect of burdock (Arctium lappa L.) root is associated with the activation of AMP-activated protein kinase in human HepG2 cells", Food Chem, 134, pp.1320~1326 (2012)