DOI QR코드

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죽력의 3T3-L1 지방전구세포에서 지방축적 억제 효과

Suppression of Lipid Accumulation in Differentiating 3T3-L1 Preadipocytes by a Standardized Commercial Juknyeok

  • 장병철 (계명대학교 의과대학 분자의학교실)
  • Jang, Byeong-Churl (Department of Molecular Medicine, College of Medicine, Keimyung University)
  • 투고 : 2022.05.17
  • 심사 : 2022.06.08
  • 발행 : 2022.06.30

초록

Objectives: Juknyeok (JN) is natural liquor extracted from bamboo stems (Phyllostachys bambusoides) and has been used as a traditional Korean medicine for improving vascular function, blood glucose, and treating stroke. Until now, the JN's lipid-lowering effect and underlying mechanism in adipocytes are poorly understood. The aim of this study was to scrutinize the effect of a standardized commercial JN on lipid accumulation during the differentiation of 3T3-L1 preadipocytes. Methods: Lipid and triglyceride (TG) accumulation in differentiating 3T3-L1 preadipocytes were measured by Oil Red O staining and AdipoRed assay, respectively. Cell count analysis was used to ascertain 3T3-L1 cytotoxicity. Immunoblotting and Reverse transcription polymerase chain reaction analysis were used to assess protein and messenger RNA (mRNA) expression levels in 3T3-L1 cells, respectively. Results: Treatment with JN at 25 𝜇l/ml after pH calibration with 6.35 significantly reduced lipid and TG accumulation in differentiating 3T3-L1 preadipocytes without significant cytotoxicity. On mechanistic levels, JN markedly suppressed protein expression levels of CCAAT/enhancer-binding protein (C/EBP)-𝛽 and fatty acid synthase (FAS) during the differentiation of 3T3-L1 preadipocytes. However, JN did not affect the protein expression levels of C/EBP-𝛼, peroxisome proliferator-activated receptor-𝛽/𝛾, and phosphorylation levels of signal transducer and activator of transcription-3/5 in differentiating 3T3-L1 preadipocytes. JN also reduced leptin mRNA expression levels in differentiating 3T3-L1 preadipocytes. Conclusions: JN at 25 𝜇l/ml lowers lipid accumulation and TG content in differentiating 3T3-L1 cells, mediated through the reduced expression levels of C/EBP-𝛽 and FAS.

키워드

과제정보

The author thanks Ms. Amila Mufida for her help in manuscript preparation.

참고문헌

  1. Fruh SM. Obesity: risk factors, complications, and strategies for sustainable long-term weight. J Am Assoc Nurse Pract. 2017 ; 29(1) : S3-S14. https://doi.org/10.1002/2327-6924.12510
  2. Aranaz P, Herrera DN, Zabala M, Migueliz I, Hualde AR, Yoldi ML, et al. Phenolic compounds inhibit 3T3-L1 adipogenesis depending on the stage of differentiation and their binding affinity to PPARγ. Molecules. 2019 ; 24(6) : 1045. https://doi.org/10.3390/molecules24061045
  3. Ellulu MS, Patimah I, Khazaai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci. 2017 ; 13(4) : 851-63.
  4. Ma X, Lee P, Chisholm DJ, James DE. Control of adipocyte differentiation in different fat depots; implications for pathophysiology or therapy. Front Endocrinol. 2015 ; 6(1) : 1-8.
  5. Berndt J, Kovacs P, Ruschke K, Kloting N, Fasshauer M, Schon MR, et al. Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes. Diabetologia. 2007 ; 50 : 1472-80. https://doi.org/10.1007/s00125-007-0689-x
  6. Cordonier EL, Jarecke SK, Hollinger FE, Zempleni J. Inhibition of acetyl-CoA carboxylases by soraphen A prevents lipid accumulation and adipocyte differentiation in 3T3-L1 cells. Eur J Pharmacol. 2016 ; 780 : 202-8. https://doi.org/10.1016/j.ejphar.2016.03.052
  7. Kern PA, Di Gregorio G, Lu T, Rassouli N, Ranganathan G. Perilipin expression in human adipose tissue is elevated with obesity. J Clin Endocrinol Metab. 2004 ; 89 : 1352-8. https://doi.org/10.1210/jc.2003-031388
  8. Panee J. Potential medicinal application and toxicity evaluation of extracts from bamboo plants. J Med Plant Res. 2015 ; 9 : 681-92. https://doi.org/10.5897/JMPR2014.5657
  9. Park EJ, Jhon DY. Effects of bamboo shoot consumption on lipid profiles and bowel function in healthy young women. Nutrition. 2009 ; 25(7-8) : 723-8. https://doi.org/10.1016/j.nut.2009.01.007
  10. Lee MJ, Park WH, Song YS, Lee YW, Song YO, Moon GS. Effect of bamboo culm extract on oxidative stress and genetic expression: bamboo culm extract ameliorates cell adhesion molecule expression and NFkappaB activity through the suppression of the oxidative stress. Clin Nutr. 2008 ; 27 : 755-63. https://doi.org/10.1016/j.clnu.2008.06.002
  11. Choi MH, Jo HG, Yang JH, Ki SH, Shin HJ. Antioxidative and anti-melanogenic activities of bamboo stems (Phyllostachys nigra variety henosis) via PKA/CREB-mediated MITF downregulation in B16F10 melanoma cells. Int J Mol Sci. 2018 ; 19 : 409. https://doi.org/10.3390/ijms19020409
  12. Jakab J, Miskic B, Miksic S, Juranic B, Cosic V, Schwarz D, et al. Adipogenesis as a potential anti-obesity target: a review of pharmacological treatment and natural products. Diabetes Metab Syndr Obes. 2021 ; 14 : 67-83. https://doi.org/10.2147/DMSO.S281186
  13. Jayarathne S, Koboziev I, Park OH, Oldewage-Theron W, Shen CL, Moustaid-Moussa N. Anti-inflammatory and anti-obesity properties of food bioactive components: effects on adipose tissue. Prev Nutr Food Sci. 2017 ; 22(4) : 251-62. https://doi.org/10.3746/pnf.2017.22.4.251
  14. Cao Z, Umek RM, McKnight SL. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991 ; 5(9) : 1538-52. https://doi.org/10.1101/gad.5.9.1538
  15. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab. 2006 ; 4(4) : 263-73. https://doi.org/10.1016/j.cmet.2006.07.001
  16. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, et al. PPARγ is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell. 1999 ; 4(4) : 611-7. https://doi.org/10.1016/S1097-2765(00)80211-7
  17. Linhart HG, Ishimura-Oka K, DeMayo F, Kibe T, Repka D, Poindexter B, et al. C/EBPα is required for differentiation of white, but not brown, adipose tissue. Proc Natl Acad Sci USA. 2001 ; 98(22) : 12532-7. https://doi.org/10.1073/pnas.211416898
  18. Stephens JM, Morrison RF, Pilch PF. The expression and regulation of STATs during 3T3-L1 adipocyte differentiation. J Biol Chem. 1996 ; 271(18) : 10441-4. https://doi.org/10.1074/jbc.271.18.10441
  19. Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, et al. C/EBPα induces adipogenesis through PPARγ: a unified pathway. Genes Dev. 2002 ; 16(1) : 22-6. https://doi.org/10.1101/gad.948702
  20. Deng J, Hua K, Lesser SS, Harp JB. Activation of signal transducer and activator of transcription-3 during proliferative phases of 3T3-L1 adipogenesis. Endocrinology. 2000 ; 141 : 2370-6. https://doi.org/10.1210/en.141.7.2370
  21. Harp JB, Franklin D, Vanderpuije AA, Gimble JM. Differential expression of signal transducers and activators of transcription during human adipogenesis. Biochem Biophys Res Commun. 2001 ; 281 : 907-12. https://doi.org/10.1006/bbrc.2001.4460
  22. Stewart WC, Morrison RF, Young SL, Stephens JM. Regulation of signal transducers and activators of transcription (STATs) by effectors of adipogenesis: coordinate regulation of STATs 1, 5A, and 5B with peroxisome proliferator-activated receptor-γ and C/AAAT enhancer binding protein-α. Biochim Biophys Acta. 1999 ; 1452 : 188-96. https://doi.org/10.1016/S0167-4889(99)00129-9
  23. Shang CA, Waters MJ. Constitutively active signal transducer and activator of transcription 5 can replace the requirement for growth hormone in adipogenesis of 3T3-F442A preadipocytes. Mol Endocrinol. 2003 ; 17 : 2494-508. https://doi.org/10.1210/me.2003-0139
  24. Ho CL, Lin CY, Ka SM, Chen A, Tasi YL, Liu ML, et al. Bamboo vinegar decreases inflammatory mediator expression and NLRP3 inflammasome activation by inhibiting reactive ocygen species generation and protein kinase C-α/δ activation. Plos One. 2013 ; 8(10) : e75738. https://doi.org/10.1371/journal.pone.0075738
  25. Higa JK, Panee J. Bamboo extract reduces interleukin 6 (IL-6) overproduction under lipotoxic conditions through inhibiting the activation of NF-kB and AP-1 pathways. Cytokine. 2011 ; 55 : 18-23. https://doi.org/10.1016/j.cyto.2011.02.019
  26. Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. The American Journal of Clinical Nutrition. 2006 ; 83 (2) : 461S-5S. https://doi.org/10.1093/ajcn/83.2.461s
  27. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduce subject. Nat Med. 1995 ; 1 : 1155-61. https://doi.org/10.1038/nm1195-1155
  28. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995 ; 269 : 543-6. https://doi.org/10.1126/science.7624777
  29. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995 ; 269 : 540-3. https://doi.org/10.1126/science.7624776
  30. Akakabe Y, Tamura Y, Iwamoto S, Takabayashi M, Nyuugaku T. Volatile organic compounds with characteristic odo in bambbo vinegar. Biosci Biotechnol Biochem. 2006 ; 70(11) : 2797-9. https://doi.org/10.1271/bbb.60317
  31. Mu J, Uehara T, Furno T. Effect of bamboo vinegar on regulation of germination and radicle growth of seed plants. J Wood Sci. 2003 ; 49 : 262-70. https://doi.org/10.1007/s10086-002-0472-z
  32. Heimann E, Nyman M, Degerman E. Propionic acid and butyric aicid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes. Adipocyte. 2015 ; 4(2) : 81-8. https://doi.org/10.4161/21623945.2014.960694
  33. Farup PG, Lydersen S, Valeur J. Are nonnutritive sweeteners obesogenic? Associatios between diet, faecal microbiota, and short-chain fatty acids in morbidly obese subjects. Journal of Obesity. 2019 ; 2019 : 4608315.