Nutrition Research and Practice

  • 제17권3호
  • /
  • Pages.438-450
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  • 2023
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  • 1976-1457(pISSN)
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  • 2005-6168(eISSN)
한국영양학회 (The Korean Nutrition Society)
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Quercetin inhibits body weight gain and adipogenesis via matrix metalloproteinases in mice fed a high-fat diet

  • SeungMin Song (Department of Food Science and Nutrition, Dankook University) ;
  • Ae Wha Ha (Department of Food Science and Nutrition, Dankook University) ;
  • WooKyoung Kim (Department of Food Science and Nutrition, Dankook University)
  • 투고 : 2022.09.14
  • 심사 : 2022.11.04
  • 발행 : 2023.06.01
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초록

BACKGROUND/OBJECTIVES: Limited studies reported that quercetin inhibited adipogenesis and neovascularization by inhibiting matrix metalloproteinases (MMPs) activity, but such mechanisms have not been elucidated in animal experiments. In this study, we investigated the inhibitory effects of quercetin on weight gain and adipose tissue growth through the regulation of mRNA expressions of adipogenic transcription factors and MMPs in mice fed a high-fat diet (HFD). MATERIALS/METHODS: Five-wk-old C57BL/6J mice were fed a normal diet (ND), HFD, HFD containing 0.05% of quercetin (HFQ0.05), or HFD containing 0.15% of quercetin (HFQ0.15) for 16 wks. Glycerol-3-phosphate dehydrogenase (GPDH) activity was measured using a commercial kit. The mRNA expressions of transcription factors related to adipocyte differentiation were determined by real-time polymerase chain reaction (PCR). The mRNA expressions of MMPs and concentrations of MMPs were measured by real-time PCR and enzyme-linked immunosorbent assay kit, respectively. RESULTS: Quercetin intake reduced body weight gain and epididymal adipose tissue weights (P < 0.05). GPDH activity was higher in the HFD group than in the ND group but lower in the quercetin groups (P < 0.05). The mRNA expressions of CCAAT/enhancer binding protein β (C/EBPβ), C/EBPα, peroxisome proliferator-activated receptor γ, and fatty acid-binding protein 4 were lower in the quercetin groups than in the HFD group (P < 0.05). Similarly, the mRNA expression and concentrations of MMP-2 and MMP-9 were significantly lower in the quercetin groups than in the HFD group (P < 0.05). CONCLUSION: The study confirms that quercetin suppresses body weight gain and adipogenesis by inhibiting transcription factors related to adipocyte differentiation and MMPs (MMP-2 and MMP-9), in mice fed a HFD.

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과제정보

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07043918).

참고문헌

  1. Korea Centers for Disease Control and Prevention. Trends in prevalence of obesity, 2011-2020. Public Health Wkly Rep 2022;15:2693-4. https://doi.org/10.56786/PHWR.2022.15.40.2693
  2. Marcelin G, Silveira AL, Martins LB, Ferreira AV, Clement K. Deciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis. J Clin Invest 2019;129:4032-40. https://doi.org/10.1172/JCI129192
  3. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011;473:298-307. https://doi.org/10.1038/nature10144
  4. Guo L, Li X, Tang QQ. Transcriptional regulation of adipocyte differentiation: a central role for CCAAT/enhancer-binding protein (C/EBP) β. J Biol Chem 2015;290:755-61. https://doi.org/10.1074/jbc.R114.619957
  5. Ali AT, Hochfeld WE, Myburgh R, Pepper MS. Adipocyte and adipogenesis. Eur J Cell Biol 2013;92:229-36. https://doi.org/10.1016/j.ejcb.2013.06.001
  6. Bellafiore M, Battaglia G, Bianco A, Farina F, Palma A, Paoli A. The involvement of MMP-2 and MMP-9 in heart exercise-related angiogenesis. J Transl Med 2013;11:283.
  7. Kruegel J, Miosge N. Basement membrane components are key players in specialized extracellular matrices. Cell Mol Life Sci 2010;67:2879-95. https://doi.org/10.1007/s00018-010-0367-x
  8. Shin SS, Yoon M. Regulation of obesity by antiangiogenic herbal medicines. Molecules 2020;25:4549.
  9. Balaji M, Ganjayi MS, Hanuma Kumar GE, Parim BN, Mopuri R, Dasari S. A review on possible therapeutic targets to contain obesity: the role of phytochemicals. Obes Res Clin Pract 2016;10:363-80. https://doi.org/10.1016/j.orcp.2015.12.004
  10. Hsu CL, Yen GC. Induction of cell apoptosis in 3T3-L1 pre-adipocytes by flavonoids is associated with their antioxidant activity. Mol Nutr Food Res 2006;50:1072-9. https://doi.org/10.1002/mnfr.200600040
  11. Hsu CL, Yen GC. Phenolic compounds: evidence for inhibitory effects against obesity and their underlying molecular signaling mechanisms. Mol Nutr Food Res 2008;52:53-61. https://doi.org/10.1002/mnfr.200700393
  12. Ku HC, Chang HH, Liu HC, Hsiao CH, Lee MJ, Hu YJ, Hung PF, Liu CW, Kao YH. Green tea (-)-epigallocatechin gallate inhibits insulin stimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor pathway. Am J Physiol Cell Physiol 2009;297:C121-32. https://doi.org/10.1152/ajpcell.00272.2008
  13. Ambati S, Yang JY, Rayalam S, Park HJ, Della-Fera MA, Baile CA. Ajoene exerts potent effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing apoptosis. Phytother Res 2009;23:513-8. https://doi.org/10.1002/ptr.2663
  14. Boccellino M, D'Angelo S. Anti-obesity effects of polyphenol intake: Current status and future possibilities. Int J Mol Sci 2020;21:5642.
  15. Yang JY, Della-Fera MA, Rayalam S, Ambati S, Hartzell DL, Park HJ, Baile CA. Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci 2008;82:1032-9. https://doi.org/10.1016/j.lfs.2008.03.003
  16. Ahn J, Lee H, Kim S, Park J, Ha T. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun 2008;373:545-9. https://doi.org/10.1016/j.bbrc.2008.06.077
  17. Hong SY, Ha AW, Kim W. Effects of quercetin on cell differentiation and adipogenesis in 3T3-L1 adipocytes. Nutr Res Pract 2021;15:444-55. https://doi.org/10.4162/nrp.2021.15.4.444
  18. Song SM, Jung SM, Choi SJ, Kim WK. Quercetin inhibits adipocyte differentiation via matrix metalloproteinases in 3T3-L1 Preadipocytes. J. Korean Soc Food Sci and Nutr. 2022;51:311-32. https://doi.org/10.3746/jkfn.2022.51.4.311
  19. Nijhawans P, Behl T, Bhardwaj S. Angiogenesis in obesity. Biomed Pharmacother 2020;126:110103.
  20. Park BS, Han SH, Lee JY, Chung YS. Evaluation of in vivo genotoxicity of plant flavonoids, quercetin and isoquercetin. J Food Hyg Saf 2016;31:356-64. https://doi.org/10.13103/JFHS.2016.31.5.356
  21. Moon J, Do HJ, Kim OY, Shin MJ. Antiobesity effects of quercetin-rich onion peel extract on the differentiation of 3T3-L1 preadipocytes and the adipogenesis in high fat-fed rats. Food Chem Toxicol 2013;58:347-54. https://doi.org/10.1016/j.fct.2013.05.006
  22. Porras D, Nistal E, Martinez-Florez S, Pisonero-Vaquero S, Olcoz JL, Jover R, Gonzalez-Gallego J, Garcia-Mediavilla MV, Sanchez-Campos S. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation. Free Radic Biol Med 2017;102:188-202. https://doi.org/10.1016/j.freeradbiomed.2016.11.037
  23. Jia Q, Cao H, Shen D, Li S, Yan L, Chen C, Xing S, Dou F. Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1. Int J Mol Med 2019;44:893-902. https://doi.org/10.3892/ijmm.2019.4263
  24. Lee JS, Cha YJ, Lee KH, Yim JE. Onion peel extract reduces the percentage of body fat in overweight and obese subjects: a 12-week, randomized, double-blind, placebo-controlled study. Nutr Res Pract 2016;10:175-81. https://doi.org/10.4162/nrp.2016.10.2.175
  25. Jung CH, Cho I, Ahn J, Jeon TI, Ha TY. Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes. Phytother Res 2013;27:139-43. https://doi.org/10.1002/ptr.4687
  26. Bae CR, Park YK, Cha YS. 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;94:2655-60. https://doi.org/10.1002/jsfa.6604
  27. Zhao X, Hu H, Wang C, Bai L, Wang Y, Wang W, Wang J. A comparison of methods for effective differentiation of the frozen-thawed 3T3-L1 cells. Anal Biochem 2019;568:57-64. https://doi.org/10.1016/j.ab.2018.12.020
  28. Boughanem H, Cabrera-Mulero A, Millan-Gomez M, Garrido-Sanchez L, Cardona F, Tinahones FJ, Moreno-Santos I, Macias-Gonzalez M. Transcriptional analysis of FOXO1, C/EBP-α and PPAR-γ2 genes and their association with obesity-related insulin resistance. Genes (Basel) 2019;10:706.
  29. Moseti D, Regassa A, Kim WK. Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int J Mol Sci 2016;17:124.
  30. Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 2011;12:722-34. https://doi.org/10.1038/nrm3198
  31. Zhang R, Qin X, Zhang T, Li Q, Zhang J, Zhao J. Astragalus polysaccharide improves insulin sensitivity via AMPK activation in 3T3-L1 adipocytes. Molecules 2018;23:2711.
  32. Bouloumie A, Sengenes C, Portolan G, Galitzky J, Lafontan M. Adipocyte produces matrix metalloproteinases 2 and 9: involvement in adipose differentiation. Diabetes 2001;50:2080-6. https://doi.org/10.2337/diabetes.50.9.2080
  33. Bauters D, Scroyen I, Van Hul M, Lijnen HR. Gelatinase A (MMP-2) promotes murine adipogenesis. Biochim Biophys Acta 2015;1850:1449-56. https://doi.org/10.1016/j.bbagen.2015.04.003
  34. Bosco DB, Roycik MD, Jin Y, Schwartz MA, Lively TJ, Zorio DA, Sang QA. A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis. PLoS One 2017;12:e0172925.
  35. Park BY, Lee H, Woo S, Yoon M, Kim J, Hong Y, Lee HS, Park EK, Hahm JC, Kim JW, et al. Reduction of adipose tissue mass by the angiogenesis inhibitor ALS-L1023 from melissa officinalis. PLoS One 2015;10:e0141612.