Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of Triacsin C on LPS-induced Inflammation in 3T3-L1 Adipocytes

LPS에 의해 유도된 3T3-L1 지방세포의 염증반응에 대한 Triacsin C의 효과

  • Park, Eun-Ju (Dept. of Food & Nutrition, Kyungnam University) ;
  • Spurlock, Michael (Dept. of Food Science and Human Nutrition, Iowa State University)
  • Received : 2012.01.26
  • Accepted : 2012.02.07
  • Published : 2012.02.29
Download PDF
⟨ Previous Next ⟩

Abstract

Triacsin C, an inhibitor of acyl-CoA synthetase, is known to have antiatherosclerotic and vasodilatory activities. The aims of this study were to evaluate the effects of triacsin C on endotoxin-induced (lipopolysaccharide, LPS) inflammation in 3T3-L1 adipocytes and also to evaluate its synergistic effect with triacsin C and resveratrol, a potent antiinflammatory agent. Exposure to LPS for 18 hr increased secretion of IL-6 into the culture medium and mRNA expression of IL-6, MCP-1, TLR and iNOS. Pretreatment of triacsin C for 2 hr suppressed IL-6 accumulation in the medium and the induction of IL-6 expression by LPS, which was more effective than resveratrol treatment. The synergistic effect of triacsin C and resveratrol was found to reduce the expression of iNOS by LPS. However, neither triacsin C nor resveratrol affected the LPS-induced expression of MCP-1, TLR or iNOS. These findings indicate that triacsin C may be a local regulator of inflammation in the adipocyte, although detailed mechanisms are needed to elucidate this through further research.

본 연구에서는 long fatty acyl CoA synthetase의 저해제이며, 죽상동맥경화 억제 및 혈관확장 효과가 있는 것으로 알려진 triacsin C의 LPS로 유도된 3T3-L1 지방세포의 염증반응에 대한 효과를 알아보고자 하였다. 10 ${\mu}M$의 triacsin C를 2시간 동안 처리한 결과, LPS로 유도된 배양액내 IL-6 분비량과 mRNA IL-6 발현이 유의적으로 감소하였고 이는 선행연구를 통해 항염증 효능이 입증된 resveratrol(50 ${\mu}M$, 24시간 처리)에 비해서도 배양액으로의 분비된 IL-6의 억제효과가 더 높게 나타났다. 그러나 triacsin C과 resveratrol의 동반상승 효과는 없는 것으로 나타났다. Triacsin C나 resveratrol은 LPS로 유도된 지방세포의 TLR2, MCP-1, iNOS 유전자 발현에 대한 억제효과는 없는 것으로 나타났다. 그러나 triacsin C 처리 후에 resveratrol을 혼합 처리한 경우 iNOS의 발현은 LPS 대조군에 비해 유의적으로 감소하였다. 향후 triacsin C가 LPS로 유도된 염증반응을 어떤 기전으로 억제하는 지에 대해서는 추후 연구가 필요한 것으로 사료된다. 결론적으로 이 연구에서는 지방산 합성 저해제인 triacsin C는 3T3-L1 지방세포에서 IL-6 특이적 항염증 효과가 있으며, triacsin C와 resveratrol을 동시에 처리했을 때 iNOS의 발현을 유의적으로 감소시킴을 확인하였다. 이는 내독소에 의한 지방세포의 염증반응에 대한 triacsin C의 항염증 효과를 입증하기 위한 기초자료로 활용이 가능할 것으로 기대된다.

Keywords

References

  1. KCDC. 2010. 2009 Korea national health and nutrition and examination survey. Ministry of health and welfare, Seoul, Korea.
  2. Douketis JD, Sharma AM. 2005. Obesity and cardiovascular disease: pathogenic mechanisms and potential benefits of weight reduction. Semin Vasc Med 5: 25-33. https://doi.org/10.1055/s-2005-871739
  3. Matsuzawaa Y, Shimomuraa I, Kiharaa S, Funahashia T. 2003. Importance of adipocytokines in obesity-related diseases. Horm Res 60: 56-59. https://doi.org/10.1159/000074502
  4. Yudkin JS. 2007. Inflammation, obesity, and the metabolic syndrome. Horm Metab Res 39: 707-709. https://doi.org/10.1055/s-2007-985898
  5. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. 2007. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56: 1761-1772. https://doi.org/10.2337/db06-1491
  6. Yu R. 2005. Modulation of obesity-related pathologies based on inflammation theory. Food Industry and Nutrition 10: 5-9.
  7. Ajuwon KM, Spurlock ME. 2005. Adiponectin inhibits LPSinduced NF-${\kappa}B$ activation and IL-6 production and increases PPAR ${\gamma}2$ expression in adipocytes. Am J Physiol Regul Integr Comp Physiol 288: R1220-R1225. https://doi.org/10.1152/ajpregu.00397.2004
  8. Ahn J, Lee H, Kim S, Ha T. 2007. Resveratrol inhibits TNF-alpha-induced changes of adipokines in 3T3-L1 adipocytes. Biochem Biophys Res Commun 364: 972-977. https://doi.org/10.1016/j.bbrc.2007.10.109
  9. Cao H, Anderson RA. 2011. Cinnamon polyphenol extract regulates tristetraprolin and related gene expression in mouse adipocytes. J Agric Food Chem 59: 2739-2744. https://doi.org/10.1021/jf103527x
  10. Lira FS, Rosa JC, Cunha CA, Ribeiro EB, do Nascimento CO, Oyama LM, Mota JF. 2011. Supplementing alpha-tocopherol (vitamin E) and vitamin D3 in high fat diet decrease IL-6 production in murine epididymal adipose tissue and 3T3-L1 adipocytes following LPS stimulation. Lipids Health Dis 10: 37-41. https://doi.org/10.1186/1476-511X-10-37
  11. Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. 2001. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280: E745-E751. https://doi.org/10.1152/ajpendo.2001.280.5.E745
  12. de Pablo MA, Alvarez de Cienfuegos G. 2000. Modulatory effects of dietary lipids on immune system functions. Immunol Cell Biol 78: 31-39. https://doi.org/10.1046/j.1440-1711.2000.00875.x
  13. Haversen L, Danielsson KN, Fogelstrand L, Wiklund O. 2009. Induction of proinflammatory cytokines by long-chain saturated fatty acids in human macrophages. Atherosclerosis 202: 382-393. https://doi.org/10.1016/j.atherosclerosis.2008.05.033
  14. Lee JY, Sohn KH, Rhee SH, Hwang D. 2001. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 276: 16683-16689. https://doi.org/10.1074/jbc.M011695200
  15. Weigert C, Brodbeck K, Staiger H, Kausch C, Machicao F, Haring HU, Schleicher ED. 2004. Palmitate, but not unsaturated fatty acids, induces the expression of interleukin-6 in human myotubes through proteasome-dependent activation of nuclear factor-kappaB. J Biol Chem 279: 23942-23952. https://doi.org/10.1074/jbc.M312692200
  16. Staiger H, Staiger K, Stefan N, Wahl HG, Machicao F, Kellerer M, Häring HU. 2004. Palmitate-induced interleukin-6 expression in human coronary artery endothelial cells. Diabetes 53: 3209-3216. https://doi.org/10.2337/diabetes.53.12.3209
  17. Ajuwon KM, Spurlock ME. 2005. Palmitate activates the NF-${\kappa}B$ transcription factor and induces IL-6 and TNF-$\alpha$ expression in 3T3-L1 adipocytes. J Nutr 135: 1841-1846. https://doi.org/10.1093/jn/135.8.1841
  18. Igal RA, Wang P, Coleman RA. 1997. Triacsin C blocks de novo synthesis of glycerolipids and cholesterol esters but not recycling of fatty acid into phospholipid: evidence for functionally separate pools of acyl-CoA. Biochem J 324: 529-534. https://doi.org/10.1042/bj3240529
  19. Namatame I, Tomoda H, Arai H, Inoue K, Omura S. 1999. Complete inhibition of mouse macrophage-derived foam cell formation by triacsin C. J Biochem 125: 319-327. https://doi.org/10.1093/oxfordjournals.jbchem.a022289
  20. Weis MT, Crumley JL, Young LH, Stallone JN. 2004. Inhibiting long chain fatty acyl CoA synthetase increases basal and agonist-stimulated NO synthesis in endothelium. Cardiovasc Res 63: 338-346. https://doi.org/10.1016/j.cardiores.2004.04.025
  21. Weis MT, Brady M, Moore M, Crumley J, Stallone JN. 2005. Inhibiting long-chain fatty acyl CoA synthetase does not increase agonist-induced release of arachidonate metabolites from human endothelial cells. J Vasc Res 42: 275-283. https://doi.org/10.1159/000085847
  22. Lin Y, Lee H, Berg AH, Lisanti MP, Shapiro L, Scherer PE. 2000. The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem 275: 24255-24263. https://doi.org/10.1074/jbc.M002137200
  23. Ajuwon KM, Jacobi SK, Kuske JL, Spurlock ME. 2004. Interleukin-6 and interleukin-15 are selectively regulated by lipopolysaccharide and interferon-γ in primary pig adipocytes. Am J Physiol Regul Integr Comp Physiol 286: R547-R553. https://doi.org/10.1152/ajpregu.00585.2003
  24. Davis JE, Gabler NK, Walker-Daniels J, Spurlock ME. 2009. The c-Jun N-terminal kinase mediates the induction of oxidative stress and insulin resistance by palmitate and toll-like receptor 2 and 4 ligands in 3T3-L1 adipocytes. Horm Metab Res 41: 523-530. https://doi.org/10.1055/s-0029-1202852
  25. Nathan C. 1997. Inducible nitric oxide synthase: what difference does it make? J Clin Invest 100: 2417-2423. https://doi.org/10.1172/JCI119782
  26. Centeno-Baez C, Dallaire P, Marette A. 2011. Resveratrol inhibition of inducible nitric oxide synthase in skeletal muscle involves AMPK but not SIRT1. Am J Physiol Endocrinol Metab 301: E922-E930. https://doi.org/10.1152/ajpendo.00530.2010