Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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North American ginseng influences adipocyte-macrophage crosstalk regulation of inflammatory gene expression

  • Garbett, Jaime (Department of Human Health and Nutritional Sciences, University of Guelph) ;
  • Wilson, Sarah A.F. (Department of Human Health and Nutritional Sciences, University of Guelph) ;
  • Ralston, Jessica C. (Department of Human Health and Nutritional Sciences, University of Guelph) ;
  • Boer, Anna A. De (Department of Human Health and Nutritional Sciences, University of Guelph) ;
  • Lui, Ed M.K. (Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University) ;
  • Wright, David C. (Department of Human Health and Nutritional Sciences, University of Guelph) ;
  • Mutch, David M. (Department of Human Health and Nutritional Sciences, University of Guelph)
  • Received : 2015.04.09
  • Accepted : 2015.07.05
  • Published : 2016.04.15
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Abstract

Background: Adipocyte-macrophage communication plays a critical role regulating white adipose tissue (WAT) inflammatory gene expression. Because WAT inflammation contributes to the development of metabolic diseases, there is significant interest in understanding how exogenous compounds regulate the adipocyte-macrophage crosstalk. An aqueous (AQ) extract of North American (NA) ginseng (Panax quinquefolius) was previously shown to have strong inflammo-regulatory properties in adipocytes. This study examined whether different ginseng extracts influence adipocyte-macrophage crosstalk, as well as WAT inflammatory gene expression. Methods: The effects of AQ and ethanol (EtOH) ginseng extracts ($5{\mu}g/mL$) on adipocyte and macrophage inflammatory gene expression were studied in 3T3-L1 and RAW264.7 cells, respectively, using real-time reverse transcription polymerase chain reaction. Adipose tissue organ culture was also used to examine the effects of ginseng extracts on epididymal WAT (EWAT) and inguinal subcutaneous WAT (SWAT) inflammatory gene expression. Results: The AQ extract caused significant increases in the expression of common inflammatory genes (e.g., Mcp1, Ccl5, Tnf-${\alpha}$, Nos2) in both cell types. Culturing adipocytes in media from macrophages treated with the AQ extract, and vice versa, also induced inflammatory gene expression. Adipocyte Ppar-${\gamma}$ expression was reduced with the AQ extract. The AQ extract strongly induced inflammatory gene expression in EWAT, but not in SWAT. The EtOH extract had no effect on inflammatory gene expression in either both cell types or WAT. Conclusion: These findings provide important new insights into the inflammo-regulatory role of NA ginseng in WAT.

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References

  1. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell 2014;156:20-44. https://doi.org/10.1016/j.cell.2013.12.012
  2. Weisberg SP, McCann D, Desai M, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796-808. https://doi.org/10.1172/JCI200319246
  3. Siriwardhana N, Kalupahana NS, Fletcher S, Xin W, Claycombe KJ, Quignard- Boulange A, Zhao L, Saxton AM, Moustaid-Moussa N. n-3 and n-6 polyunsaturated fatty acids differentially regulate adipose angiotensinogen and other inflammatory adipokines in part via $NF-{\kappa}B$-dependent mechanisms. J Nutr Biochem 2012;23:1661-7. https://doi.org/10.1016/j.jnutbio.2011.11.009
  4. Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report 2008;12:1-23.
  5. Wilson SA, Wong MH, Stryjecki C, De Boer A, Lui EM, Mutch DM. Unraveling the adipocyte inflammomodulatory pathways activated by North American ginseng. Int J Obes (Lond) 2013;37:350-6. https://doi.org/10.1038/ijo.2012.50
  6. Shergis JL, Zhang AL, Zhou W, Xue CC. Panax ginseng in randomised controlled trials: a systematic review. Phytother Res 2013;27:949-65. https://doi.org/10.1002/ptr.4832
  7. Nakaya TA, Kita M, Kuriyama H, Iwakura Y, Imanishi J. Panax ginseng induces production of proinflammatory cytokines via toll-like receptor. J Interferon Cytokine Res 2004;24:93-100. https://doi.org/10.1089/107999004322813336
  8. Azike CG, Charpentier PA, Hou J, Pei H, King Lui EM. The Yin and Yang actions of North American ginseng root in modulating the immune function of macrophages. Chin Med 2011;6:21. https://doi.org/10.1186/1749-8546-6-21
  9. Azike CG, Charpentier PA, Lui EM. Stimulation and suppression of innate immune function by American ginseng polysaccharides: biological relevance and identification of bioactives. Pharm Res 2015;32:876-97. https://doi.org/10.1007/s11095-014-1503-3
  10. Vallone PM, Butler JM. AutoDimer: a screening tool for primer-dimer and hairpin structures. Biotechniques 2004;37:226-31. https://doi.org/10.2144/04372ST03
  11. Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003;3:23-35. https://doi.org/10.1038/nri978
  12. Arner P. Regional differences in protein production by human adipose tissue. Biochem Soc Trans 2001;29:72-5. https://doi.org/10.1042/bst0290072
  13. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004;145:2273-82. https://doi.org/10.1210/en.2003-1336
  14. Suganami T, Nishida J, Ogawa Y. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 2005;25:2062-8. https://doi.org/10.1161/01.ATV.0000183883.72263.13
  15. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011;11:85-97. https://doi.org/10.1038/nri2921
  16. Chawla A, Nguyen KD, Goh YP. Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol 2011;11:738-49. https://doi.org/10.1038/nri3071
  17. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007;117:175-84. https://doi.org/10.1172/JCI29881
  18. Wu H, Ghosh S, Perrard XD, Feng L, Garcia GE, Perrard JL, Sweeney JF, Peterson LE, Chan L, Smith CW, et al. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 2007;115:1029-38. https://doi.org/10.1161/CIRCULATIONAHA.106.638379
  19. Yang JW, Kim SS. Ginsenoside Rc promotes anti-adipogenic activity on 3T3-L1 adipocytes by down-regulating $C/EBP{\alpha}$ and $PPAR{\gamma}$. Molecules 2015;20:1293-303. https://doi.org/10.3390/molecules20011293
  20. Zhang Y, Yu L, Cai W, Fan S, Feng L, Ji G, Huang C. Protopanaxatriol, a novel $PPAR{\gamma}$ antagonist from Panax ginseng, alleviates steatosis in mice. Sci Rep 2014;4:7375. http://dx.doi.org/10.1038/srep07375.
  21. Sell H, Eckardt K, Taube A, Tews D, Gurgui M, Van Echten-Deckert G, Eckel J. Skeletal muscle insulin resistance induced by adipocyte-conditioned medium: underlying mechanisms and reversibility. Am J Physiol Endocrinol Metab 2008;294:E1070-7. https://doi.org/10.1152/ajpendo.00529.2007
  22. Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 2007;56:1010-3. https://doi.org/10.2337/db06-1656
  23. Samaras K, Botelho NK, Chisholm DJ, Lord RV. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring) 2010;18:884-9. https://doi.org/10.1038/oby.2009.443
  24. Cancello R, Tordjman J, Poitou C, Guilhem G, Bouillot JL, Hugol D, Coussieu C, Basdevant A, Bar Hen A, Bedossa P, et al. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes 2006;55:1554-61. https://doi.org/10.2337/db06-0133
  25. Einstein FH, Atzmon G, Yang XM, Ma XH, Rincon M, Rudin E, Muzumdar R, Barzilai N. Differential responses of visceral and subcutaneous fat depots to nutrients. Diabetes 2005;54:672-8. https://doi.org/10.2337/diabetes.54.3.672
  26. Rokling-Andersen MH, Rustan AC, Wensaas AJ, Kaalhus O, Wergedahl H, Rost TH, Jensen J, Graff BA, Caesar R, Drevon CA. Marine n-3 fatty acids promote size reduction of visceral adipose depots, without altering body weight and composition, in male Wistar rats fed a high-fat diet. Br J Nutr 2009;102:995-1006. https://doi.org/10.1017/S0007114509353210

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