Genistein and Daidzein Repress Adipogenic Differentiation of Human Adipose Tissue-derived Mesenchymal Stem Cells Via Wnt/β-catenin Signalling or Lipolysis

Overview

Journal Cell Prolif

Date 2010 Nov 3

PMID 21039998

Citations 27

Authors

M-H Kim

J-S Park

M-S Seo

J-W Jung

Y-S Lee

K-S Kang

Affiliations

Soon will be listed here.

Abstract

Objectives: One aspect of the effects of isoflavones against fat deposition might be at least associated with the mechanism by which Wnt/β-catenin signalling inhibits adipocyte differentiation. However, it remains completely unknown as to whether isoflavones might influence Wnt signalling during commitment of pluripotent mesenchymal stem cells (MSCs) to adipose lineages. In the present study, we have investigated the mechanisms underlying effects of genistein and daidzein, the major soy isoflavones, on anti-adipogenic Wnt/β-catenin signalling.

Materials And Methods: Adipose tissue-derived (AD) MSCs were exposed continuously to genistein and daidzein (0.01-100 μm) during adipogenic differentiation (21 days). An oestrogen antagonist, ICI 182,780, was used to determine whether or not the isoflavones activated Wnt signalling via oestrogen receptors (ERs).

Results: Genistein and daidzein suppressed adipogenic differentiation of AD-MSCs in a dose-dependent manner and inhibited expression of adipogenic markers, PPARγ, SREBP-1c and Glut 4, from mid-phase differentiation. Microarrays showed that anti-adipogenic effects of genistein were principally attributable to activation of Wnt signalling via ERs-dependent pathway, such as Erk/JNK signalling and LEF/TCF4 co-activators. These findings were supported by evidence that the effects of genistein were offset by ICI182,780. Unlike genistein, daidzein inhibited adipogenesis through stimulation of lipolysis, with for example, PKA-mediated hormone sensitive lipase. This is consistent with the increase in glycerol released from AD-MSCs. In conclusion, understanding that different sets of mechanisms of the two isoflavones on adipogenesis will help the design of novel strategies to prevent observed current epidemic levels of obesity, using isoflavones.

Citing Articles

Effects of Soybean Extracts Prepared with Bionuruk on Adipogenesis in 3T3-L1 Adipocytes.

Kim H, Chung H Prev Nutr Food Sci. 2025; 30(1):28-36.

PMID: 40059913 PMC: 11884942. DOI: 10.3746/pnf.2025.30.1.28.

Crosstalk between adipogenesis and aging: role of polyphenols in combating adipogenic-associated aging.

Al-Regaiey K Immun Ageing. 2024; 21(1):76.

PMID: 39511615 PMC: 11542427. DOI: 10.1186/s12979-024-00481-w.

Sulforaphane Ameliorates High-Fat-Diet-Induced Metabolic Abnormalities in Young and Middle-Aged Obese Male Mice.

Luo J, Alkhalidy H, Jia Z, Liu D Foods. 2024; 13(7).

PMID: 38611359 PMC: 11012181. DOI: 10.3390/foods13071055.

A review of the role of liposome-encapsulated phytochemicals targeting PPAR Ɣ and associated pathways to combat obesity.

Shaji A, Jayasri M 3 Biotech. 2023; 13(9):313.

PMID: 37636999 PMC: 10449732. DOI: 10.1007/s13205-023-03740-7.

Genistein ameliorated experimentally induced gastric ulcer in rats via inhibiting gastric tissues fibrosis by modulating Wnt/β-catenin/TGF-β/PKB pathway.

Hassan H, Alatawi N, Bagalagel A, Diri R, Noor A, Almasri D Redox Rep. 2023; 28(1):2218679.

PMID: 37260037 PMC: 10236962. DOI: 10.1080/13510002.2023.2218679.

References

Miyakoshi T, Kajiya H, Miyajima K, Takei M, Tobita M, Takekoshi S . The expression of Wnt4 is regulated by estrogen via an estrogen receptor alpha-dependent pathway in rat pituitary growth hormone-producing cells. Acta Histochem Cytochem. 2010; 42(6):205-13. PMC: 2808504. DOI: 10.1267/ahc.09033. View

Noble M, Smith J, Power J, Mayer-Proschel M . Redox state as a central modulator of precursor cell function. Ann N Y Acad Sci. 2003; 991:251-71. DOI: 10.1111/j.1749-6632.2003.tb07481.x. View

Du J, Zhang L, Wang Z . Testosterone inhibits the activity of peroxisome proliferator-activated receptor gamma in a transcriptional transaction assay. Pharmazie. 2009; 64(10):692-3. View

Bhat R, Stauffer B, Komm B, Bodine P . Structure-function analysis of secreted frizzled-related protein-1 for its Wnt antagonist function. J Cell Biochem. 2007; 102(6):1519-28. DOI: 10.1002/jcb.21372. View

Mei B, Zhao L, Chen L, Sul H . Only the large soluble form of preadipocyte factor-1 (Pref-1), but not the small soluble and membrane forms, inhibits adipocyte differentiation: role of alternative splicing. Biochem J. 2002; 364(Pt 1):137-44. PMC: 1222555. DOI: 10.1042/bj3640137. View

Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A . LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001; 411(6835):321-5. DOI: 10.1038/35077108. View

Camp H, Tafuri S, Leff T . c-Jun N-terminal kinase phosphorylates peroxisome proliferator-activated receptor-gamma1 and negatively regulates its transcriptional activity. Endocrinology. 1999; 140(1):392-7. DOI: 10.1210/endo.140.1.6457. View

Arner P . Effects of testosterone on fat cell lipolysis. Species differences and possible role in polycystic ovarian syndrome. Biochimie. 2005; 87(1):39-43. DOI: 10.1016/j.biochi.2004.11.012. View

Hu E, Kim J, Sarraf P, Spiegelman B . Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma. Science. 1996; 274(5295):2100-3. DOI: 10.1126/science.274.5295.2100. View

10.

Ding Q, Xia W, Liu J, Yang J, Lee D, Xia J . Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin. Mol Cell. 2005; 19(2):159-70. DOI: 10.1016/j.molcel.2005.06.009. View

11.

Weyer C, Foley J, Bogardus C, Tataranni P, Pratley R . Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia. 2001; 43(12):1498-506. DOI: 10.1007/s001250051560. View

12.

Hwang J, Park I, Shin J, Lee Y, Lee S, Baik H . Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun. 2005; 338(2):694-9. DOI: 10.1016/j.bbrc.2005.09.195. View

13.

Lin T, Tsai J, Lin S, Lai C, Chang C . Accelerated growth and prolonged lifespan of adipose tissue-derived human mesenchymal stem cells in a medium using reduced calcium and antioxidants. Stem Cells Dev. 2005; 14(1):92-102. DOI: 10.1089/scd.2005.14.92. View

14.

Aragno M, Tomasinelli C, Vercellinatto I, Catalano M, Collino M, Fantozzi R . SREBP-1c in nonalcoholic fatty liver disease induced by Western-type high-fat diet plus fructose in rats. Free Radic Biol Med. 2009; 47(7):1067-74. DOI: 10.1016/j.freeradbiomed.2009.07.016. View

15.

Chepda T, Cadau M, Girin P, Frey J, Chamson A . Monitoring of ascorbate at a constant rate in cell culture: effect on cell growth. In Vitro Cell Dev Biol Anim. 2001; 37(1):26-30. DOI: 10.1290/1071-2690(2001)037<0026:MOAAAC>2.0.CO;2. View

16.

Amit S, Hatzubai A, Birman Y, Andersen J, Ben-Shushan E, Mann M . Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev. 2002; 16(9):1066-76. PMC: 186245. DOI: 10.1101/gad.230302. View

17.

Lamartiniere C, Eltoum I, Greenberg N, Elgavish A . Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP). Cancer Res. 2001; 61(18):6777-82. View

18.

Kanazawa A, Tsukada S, Kamiyama M, Yanagimoto T, Nakajima M, Maeda S . Wnt5b partially inhibits canonical Wnt/beta-catenin signaling pathway and promotes adipogenesis in 3T3-L1 preadipocytes. Biochem Biophys Res Commun. 2005; 330(2):505-10. DOI: 10.1016/j.bbrc.2005.03.007. View

19.

Gustafson B, Smith U . Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes. J Biol Chem. 2006; 281(14):9507-16. DOI: 10.1074/jbc.M512077200. View

20.

Jain N, Thatte J, Braciale T, Ley K, OConnell M, Lee J . Local-pooled-error test for identifying differentially expressed genes with a small number of replicated microarrays. Bioinformatics. 2003; 19(15):1945-51. DOI: 10.1093/bioinformatics/btg264. View