Skip to main content
SpringerLink
Log in

Ethanolic extract of Sargassum serratifolium inhibits adipogenesis in 3T3-L1 preadipocytes by cell cycle arrest

  • Published:
Journal of Applied Phycology Aims and scope Submit manuscript

Abstract

The brown alga, Sargassum serratifolium C. Agardh, has been reported to have high levels of meroterpenoids having anti-inflammatory, antioxidant, and anti-diabetic activities. This study investigated the effect of ethanolic extract of S. serratifolium (ESS) on the inhibition of adipogenesis and lipid accumulation in 3T3-L1 preadipocytes. ESS suppressed the accumulation of lipid droplets and triglycerides (TG), while enhancing the lipolysis of intracellular TG. We found that ESS induced cell cycle arrest at the G1/S phase via suppressing protein expression of cyclin-dependent kinases (CDK) 2, CDK4, CDK6, and cyclin E. Moreover, ESS reduced the expression of CCAAT/enhancer-binding protein (C/EBP) β during the early stage of adipogenesis, leading to suppressed expression of both messenger RNA (mRNA) and protein of C/EBPα and peroxisome proliferator-activated receptor γ. As a result, ESS reduced mRNA and protein levels of lipogenic transcription factors such as retinoid X receptor, and sterol regulatory element-binding protein 1c and their target genes, such as fatty acid synthase and stearoyl-CoA desaturase (SCD) 1. Overall, ESS inhibited adipocyte differentiation in early stage and lipid accumulation during adipogenesis through downregulation of adipogenic and lipogenic transcription factors, providing the anti-obesity mechanism of ESS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Auld CA, Caccia CD, Morrison RF (2007) Hormonal induction of adipogenesis induces Skp2 expression through PI3K and MAPK pathways. J Cell Biochem 100:204–216

    Article  CAS  PubMed  Google Scholar 

  • Bost F, Aouadi M, Caron L, Even P, Belmonte N, Prot M, Dani C, Hofman P, Pages G, Pouyssegur J, Le Marchand-Brustel Y, Binetruy B (2005) The extracellular signal-regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis. Diabetes 54:402–411

    Article  CAS  PubMed  Google Scholar 

  • Chae SY, Seo SG, Yang H, Yu JG, Suk SJ, Jung ES, Ji H, Kwon JY, Lee HJ, Lee KW (2015) Anti-adipogenic effect of erucin in early stage of adipogenesis by regulating Ras activity in 3T3-L1 preadipocytes. J Funct Foods 19:700–709

    Article  CAS  Google Scholar 

  • Chen C-C, Chuang W-T, Lin A-H, Tsai C-W, Huang C-S, Chen Y-T, Chen H-W, Lii C-K (2016) Andrographolide inhibits adipogenesis of 3T3-L1 cells by suppressing C/EBPβ expression and activation. Toxicol Appl Pharmacol 307:115–122

    Article  CAS  PubMed  Google Scholar 

  • Christy RJ, Yang VW, Ntambi JM, Geiman DE, Landschulz WH, Friedman AD, Nakabeppu Y, Kelly TJ, Lane MD (1989) Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev 3:1323–1335

    Article  CAS  PubMed  Google Scholar 

  • Foufelle F, Ferre P (2002) New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. Biochem J 366:377–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gwon WG, Lee B, Joung EJ, Choi MW, Yoon N, Shin T, Oh CW, Kim HR (2015) Sargaquinoic acid inhibits TNF-α-induced NF-κB signaling, thereby contributing to decreased monocyte adhesion to human umbilical vein endothelial cells (HUVECs). J Agric Food Chem 63:9053–9061

    Article  CAS  PubMed  Google Scholar 

  • Gwon WG, Joung EJ, Kwon MS, Lim SJ, Utsuki T, Kim HR (2017) Sargachromenol protects against vascular inflammation by preventing TNF-alpha-induced monocyte adhesion to primary endothelial cells via inhibition of NF-kappaB activation. Int Immunopharmacol 42:81–89

    Article  CAS  PubMed  Google Scholar 

  • Hamza MS, Pott S, Vega VB, Thomsen JS, Kandhadayar GS, Ng PW, Chiu KP, Pettersson S, Wei CL, Ruan Y, Liu ET (2009) De-novo identification of PPARγ/RXR binding sites and direct targets during adipogenesis. PLoS One 4(3):e4907

    Article  PubMed  PubMed Central  Google Scholar 

  • He Y, Niu W, Xia C, Cao B (2016) Daidzein reduces the proliferation and adiposeness of 3T3-L1 preadipocytes via regulating adipogenic gene expression. J Funct Foods 22:446–453

    Article  CAS  Google Scholar 

  • Joung EJ, Gwon WG, Shin TS, Jung BM, Choi JS, Kim HR (2017) Anti-inflammatory action of the ethanolic extract from Sargassum serratifolium on lipopolysaccharide-stimulated mouse peritoneal macrophages and identification of active components. J Appl Phycol 29:563–573

    Article  CAS  Google Scholar 

  • Jung HA, Jung HJ, Jeong HY, Kwon HJ, Kim MS, Choi JS (2014) Anti-adipogenic activity of the edible brown alga Ecklonia stolonifera and its constituent fucosterol in 3T3-L1 adipocytes. Arch Pharm Res 37:713–720

    Article  CAS  PubMed  Google Scholar 

  • Kang MC, Kang N, Ko SC, Kim YB, Jeon YJ (2016) Anti-obesity effects of seaweeds of Jeju Island on the differentiation of 3T3-L1 preadipocytes and obese mice fed a high-fat diet. Food Chem Toxicol 90:36–44

    Article  CAS  PubMed  Google Scholar 

  • Kim JB, Spiegelman BM (1996) ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev 10:1096–1107

    Article  CAS  PubMed  Google Scholar 

  • Kim SN, Choi HY, Lee W, Park GM, Shin WS, Kim YK (2008) Sargaquinoic acid and sargahydroquinoic acid from Sargassum yezoense stimulate adipocyte differentiation through PPARα/γ activation in 3T3-L1 cells. FEBS Lett 582:3465–3472

    Article  CAS  PubMed  Google Scholar 

  • Kim JA, Karadeniz F, Ahn BN, Kwon MS, Mun OJ, Bae MJ, Seo Y, Kim M, Lee SH, Kim YY, Mi-Soon J, Kong CS (2015) Bioactive quinone derivatives from the marine brown alga Sargassum thunbergii induce anti-adipogenic and pro-osteoblastogenic activities. J Sci Food Agric. doi:10.1002/jsfa.7148

  • Lane MD, Tang QQ, Jiang MS (1999) Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation. Biochem Biophys Res Commun 266:677–683

  • Li X, Kim JW, Grønborg M, Urlaub H, Lane MD, Tang Q-Q (2007) Role of cdk2 in the sequential phosphorylation/activation of C/EBPβ during adipocyte differentiation. Proc Nat Acad Sci USA 104:11597–11602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma AC, Chen Z, Wang T, Song N, Yan Q, Fang YC, Guan HS, Liu HB (2014) Isolation of the molecular species of monogalactosyldiacylglycerols from brown edible seaweed Sargassum horneri and their inhibitory effects on triglyceride accumulation in 3T3-L1 adipocytes. J Agric Food Chem 62:11157–11162

  • Ntambi JM, Young-Cheul K (2000) Adipocyte differentiation and gene expression. J Nutr 130:3122s–3126s

    Article  CAS  PubMed  Google Scholar 

  • Oh SJ, Joung EJ, Kwon MS, Lee B, Utsuki T, Oh CW, Kim HR (2016) Anti-inflammatory effect of ethanolic extract of Sargassum serratifolium in lipopolysaccharide-stimulated BV2 microglial cells. J Med Food 19:1023–1031

    Article  CAS  PubMed  Google Scholar 

  • Park H, Cho JA, Lim EH, Lee CW, Lee SH, Won Seo S, Yang DY, Lee KW (2011) Cell cycle regulators are critical for maintaining the differentiation potential and immaturity in adipogenesis of adipose-derived stem cells. Differentiation 82:136–143

    Article  CAS  PubMed  Google Scholar 

  • Richard AJ, Stephens JM (2014) The role of JAK-STAT signaling in adipose tissue function. Biochim Biophys Acta 1842:431–439

    Article  CAS  PubMed  Google Scholar 

  • Rosen ED, Spiegelman BM (2001) PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 276:37731–37734

    Article  CAS  PubMed  Google Scholar 

  • Takada I, Suzawa M, Matsumoto K, Kato S (2007) Suppression of PPAR transactivation switches cell fate of bone marrow stem cells from adipocytes into osteoblasts. Ann N Y Acad Sci 1116:182–195

    Article  CAS  PubMed  Google Scholar 

  • Tang QQ, Otto TC, Lane MD (2003) Mitotic clonal expansion: a synchronous process required for adipogenesis. Proc Nat Acad Sci USA 100:44–49

    Article  CAS  PubMed  Google Scholar 

  • Tang QQ, Gronborg M, Huang H, Kim JW, Otto TC, Pandey A, Lane MD (2005) Sequential phosphorylation of CCAAT enhancer-binding protein beta by MAPK and glycogen synthase kinase 3β is required for adipogenesis. Proc Nat Acad Sci USA 102:9766–9771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang D, Zhou Y, Lei W, Zhang K, Shi J, Hu Y, Shu G, Song J (2009) Signal transducer and activator of transcription 3 (STAT3) regulates adipocyte differentiation via peroxisome-proliferator-activated receptor γ (PPARγ). Biol Cell 102:1–12

    Article  PubMed  Google Scholar 

  • Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M (2011) Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 378:815–825

    Article  PubMed  Google Scholar 

  • Wu C-H, Pan C-H, Lee C-K, Sheu M-J, Liu F-C, Wang G-J, Wu C-H (2016) Antiobesity and antihyperlipidaemic effects of Yan-Sheng-Yin in animals and humans. J Funct Foods 24:173–182

    Article  CAS  Google Scholar 

  • Yeh WC, Bierer BE, McKnight SL (1995) Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells. Proc Nat Acad Sci USA 92:11086–11090

  • Yim MJ, Hosokawa M, Mizushina Y, Yoshida H, Saito Y, Miyashita K (2011) Suppressive effects of amarouciaxanthin A on 3T3-L1 adipocyte differentiation through down-regulation of PPARγ and C/EBPα mRNA expression. J Agric Food Chem 59:1646–1652

    Article  CAS  PubMed  Google Scholar 

  • Zhang JW, Klemm DJ, Vinson C, Lane MD (2004) Role of CREB in transcriptional regulation of CCAAT/enhancer-binding protein β gene during adipogenesis. J Biol Chem 279:4471–4478

  • Zhang K, Guo W, Yang Y, Wu J (2011) JAK2/STAT3 pathway is involved in the early stage of adipogenesis through regulating C/EBPβ transcription. J Cell Biochem 112:488–497

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Tang H, Deng R, Wang N, Zhang Y, Wang Y, Liu Y, Li F, Wang X, Zhou L (2015) Berberine suppresses adipocyte differentiation via decreasing CREB transcriptional activity. PLoS One 10(4):e0125667

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This research was supported by the project “Development of nutraceuticals from Sargassum serratifolium” funded by the Ministry of Oceans and Fisheries, Republic of Korea.

Author information

Authors and Affiliations

  1. Department of Food Science and Nutrition, Pukyong National University, 45, Yongso-Ro, Nam-Gu, Busan, 48513, Republic of Korea

    Misung Kwon, Su-Jin Lim & Hyeung-Rak Kim

  2. Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), 70, Cheomdan-Ro, Dong-Gu, Daegu, 41068, Republic of Korea

    Bonggi Lee

  3. Division of Food and Nutrition, Chonnam National University, 77, Yongbong-Ro, Buk-Gu, Gwangju, 61186, Republic of Korea

    Taisun Shin

Authors
  1. Misung Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Su-Jin Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bonggi Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Taisun Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyeung-Rak Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hyeung-Rak Kim.

Electronic supplementary material

ESM 1

(DOCX 44 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kwon, M., Lim, SJ., Lee, B. et al. Ethanolic extract of Sargassum serratifolium inhibits adipogenesis in 3T3-L1 preadipocytes by cell cycle arrest. J Appl Phycol 30, 559–568 (2018). https://doi.org/10.1007/s10811-017-1215-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10811-017-1215-2

Keywords

Search

Navigation