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The protective effects of steamed ginger on adipogenesis in 3T3-L1 cells and adiposity in diet-induced obese mice

  • Kim, Bohkyung (Department of Food Science and Nutrition, Pusan National University) ;
  • Kim, Hee-Jeong (Department of Food Science and Human Nutrition and Obesity Research Center, Jeonbuk National University) ;
  • Cha, Youn-Soo (Department of Food Science and Human Nutrition and Obesity Research Center, Jeonbuk National University)
  • Received : 2019.11.07
  • Accepted : 2020.11.25
  • Published : 2021.06.01

Abstract

BACKGROUND/OBJECTIVES: The steamed ginger has been shown to have antioxidative effects and a protective effect against obesity. In the present study, we investigated the effects of ethanolic extract of steamed ginger (SGE) on adipogenesis in 3T3-L1 preadipocytes and diet-induced obesity (DIO) mouse model. MATERIALS/METHODS: The protective effects of SGE on adipogenesis were examined in 3T3-L1 adipocytes by measuring lipid accumulations and genes involved in adipogenesis. Male C57BL/6J mice were fed a normal diet (ND, 10% fat w/w), a high-fat diet (HFD, 60% fat w/w), and HFD supplemented with either 40 mg/kg or 80 mg/kg of SGE for 12 weeks. Serum chemistry was measured, and the expression of genes involved in lipid metabolism was determined in the adipose tissue. Histological analysis and micro-computed tomography were performed to identify lipid accumulations in epididymal fat pads. RESULTS: In 3T3-L1 cells, SGE significantly decreased lipid accumulation, with concomitant decreases in the expression of adipogenesis-related genes. SGE significantly attenuated the increase in body, liver, and epididymal adipose tissue weights by HFD. Serum total cholesterol and triglyceride levels were significantly lower in SGE fed groups compared to HFD. In adipose tissue, SGE significantly decreased adipocyte size than that of HFD and altered adipogenesis-related genes. CONCLUSIONS: In conclusion, steamed ginger exerted anti-obesity effects by regulating genes involved in adipogenesis and lipogenesis in 3T3-L1 cell and epididymal adipose tissue of DIO mice.

Keywords

Acknowledgement

This work was supported by the Ministry of Agriculture, Food and Rural Affairs (MAFRA), through the 2015 Healthy Local Food Branding Project of the Rural Resources Complex Industrialization Support Program.

References

  1. Botchlett R, Woo SL, Liu M, Pei Y, Guo X, Li H, Wu C. Nutritional approaches for managing obesity-associated metabolic diseases. J Endocrinol 2017;233:R145-71. https://doi.org/10.1530/JOE-16-0580
  2. Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, Cushman SW, Periwal V. Hypertrophy and/or hyperplasia: dynamics of adipose tissue growth. PLOS Comput Biol 2009;5:e1000324. https://doi.org/10.1371/journal.pcbi.1000324
  3. Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Front Endocrinol (Lausanne) 2016;7:30. https://doi.org/10.3389/fendo.2016.00030
  4. Nishimura S, Manabe I, Nagasaki M, Hosoya Y, Yamashita H, Fujita H, Ohsugi M, Tobe K, Kadowaki T, Nagai R, Sugiura S. Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels. Diabetes 2007;56:1517-26. https://doi.org/10.2337/db06-1749
  5. Haczeyni F, Bell-Anderson KS, Farrell GC. Causes and mechanisms of adipocyte enlargement and adipose expansion. Obes Rev 2018;19:406-20. https://doi.org/10.1111/obr.12646
  6. Tandon P, Wafer R, Minchin JE. Adipose morphology and metabolic disease. J Exp Biol 2018;221 Suppl 1:221.
  7. Roberts R, Hodson L, Dennis AL, Neville MJ, Humphreys SM, Harnden KE, Micklem KJ, Frayn KN. Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans. Diabetologia 2009;52:882-90. https://doi.org/10.1007/s00125-009-1300-4
  8. 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
  9. Mota de Sa P, Richard AJ, Hang H, Stephens JM. Transcriptional regulation of adipogenesis. Compr Physiol 2017;7:635-74.
  10. Siersbaek R, Nielsen R, Mandrup S. PPARgamma in adipocyte differentiation and metabolism--novel insights from genome-wide studies. FEBS Lett 2010;584:3242-9. https://doi.org/10.1016/j.febslet.2010.06.010
  11. Musri MM, Parrizas M. Epigenetic regulation of adipogenesis. Curr Opin Clin Nutr Metab Care 2012;15:342-9. https://doi.org/10.1097/MCO.0b013e3283546fba
  12. Liu Y, Sun M, Yao H, Liu Y, Gao R. Herbal medicine for the treatment of obesity: an overview of scientific evidence from 2007 to 2017. Evid Based Complement Alternat Med 2017;2017:8943059.
  13. Choi JY, Kim YJ, Cho SJ, Kwon EY, Ryu R, Choi MS. Metabolic effect of an oriental herbal medicine on obesity and its comorbidities with transcriptional responses in diet-induced obese mice. Int J Mol Sci 2017;18:18. https://doi.org/10.3390/ijms18010018
  14. Ebrahimzadeh Attari V, Malek Mahdavi A, Javadivala Z, Mahluji S, Zununi Vahed S, Ostadrahimi A. A systematic review of the anti-obesity and weight lowering effect of ginger (Zingiber officinale Roscoe) and its mechanisms of action. Phytother Res 2018;32:577-85. https://doi.org/10.1002/ptr.5986
  15. Wang J, Ke W, Bao R, Hu X, Chen F. Beneficial effects of ginger Zingiber officinale Roscoe on obesity and metabolic syndrome: a review. Ann N Y Acad Sci 2017;1398:83-98. https://doi.org/10.1111/nyas.13375
  16. Ali BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol 2008;46:409-20. https://doi.org/10.1016/j.fct.2007.09.085
  17. Lau AJ, Seo BH, Woo SO, Koh HL. High-performance liquid chromatographic method with quantitative comparisons of whole chromatograms of raw and steamed Panax notoginseng. J Chromatogr A 2004;1057:141-9. https://doi.org/10.1016/j.chroma.2004.09.069
  18. Toh DF, New LS, Koh HL, Chan EC. Ultra-high performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOFMS) for time-dependent profiling of raw and steamed Panax notoginseng. J Pharm Biomed Anal 2010;52:43-50. https://doi.org/10.1016/j.jpba.2009.12.005
  19. Toh DF, Patel DN, Chan EC, Teo A, Neo SY, Koh HL. Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells. Chin Med 2011;6:4. https://doi.org/10.1186/1749-8546-6-4
  20. Yoo KY, Lee CH, Li H, Park JH, Choi JH, Hwang IK, Kang IJ, Won MH. Ethyl acetate extracts of raw and steamed Codonopsis lanceolata protects against ischemic damage potentially by maintaining SOD1 and BDNF levels. Int J Neurosci 2011;121:503-9. https://doi.org/10.3109/00207454.2011.580867
  21. Ho SC, Su MS. Evaluating the anti-neuroinflammatory capacity of raw and steamed garlic as well as five organosulfur compounds. Molecules 2014;19:17697-714. https://doi.org/10.3390/molecules191117697
  22. Noda Y, Asada C, Sasaki C, Hashimoto S, Nakamura Y. Extraction method for increasing antioxidant activity of raw garlic using steam explosion. Biochem Eng J 2013;73:1-4. https://doi.org/10.1016/j.bej.2013.01.013
  23. Cheng XL, Liu Q, Peng YB, Qi LW, Li P. Steamed ginger (Zingiber officinale): changed chemical profile and increased anticancer potential. Food Chem 2011;129:1785-92. https://doi.org/10.1016/j.foodchem.2011.06.026
  24. Iwasaki Y, Morita A, Iwasawa T, Kobata K, Sekiwa Y, Morimitsu Y, Kubota K, Watanabe T. A nonpungent component of steamed ginger--[10]-shogaol--increases adrenaline secretion via the activation of TRPV1. Nutr Neurosci 2006;9:169-78. https://doi.org/10.1080/10284150600955164
  25. Kim HJ, Kim B, Mun EG, Jeong SY, Cha YS. The antioxidant activity of steamed ginger and its protective effects on obesity induced by high-fat diet in C57BL/6J mice. Nutr Res Pract 2018;12:503-11. https://doi.org/10.4162/nrp.2018.12.6.503
  26. Park SH, Jung SJ, Choi EK, Ha KC, Baek HI, Park YK, Han KH, Jeong SY, Oh JH, Cha YS, Park BH, Chae SW. The effects of steamed ginger ethanolic extract on weight and body fat loss: a randomized, doubleblind, placebo-controlled clinical trial. Food Sci Biotechnol 2019;29:265-73. https://doi.org/10.1007/s10068-019-00649-x
  27. Thomas SS, Kim M, Lee SJ, Cha YS. Antiobesity effects of purple perilla (Perilla frutescens var. acuta) on adipocyte differentiation and mice fed a high-fat diet. J Food Sci 2018;83:2384-93. https://doi.org/10.1111/1750-3841.14288
  28. Kim M, Song SB, Cha YS. Effects of black adzuki bean (Vigna angularis, Geomguseul) extract on body composition and hypothalamic neuropeptide expression in rats fed a high-fat diet. Food Nutr Res 2015;59:27719. https://doi.org/10.3402/fnr.v59.27719
  29. Kim M, Park JE, Song SB, Cha YS. Effects of black adzuki bean (Vigna angularis) extract on proliferation and differentiation of 3T3-L1 preadipocytes into mature adipocytes. Nutrients 2015;7:277-92. https://doi.org/10.3390/nu7010277
  30. Campos CF, Duarte MS, Guimaraes SE, Verardo LL, Wei S, Du M, Jiang Z, Bergen WG, Hausman GJ, Fernyhough-Culver M, Albrecht E, Dodson MV. Review: animal model and the current understanding of molecule dynamics of adipogenesis. Animal 2016;10:927-32. https://doi.org/10.1017/S1751731115002992
  31. Li HX, Xiao L, Wang C, Gao JL, Zhai YG. Review: epigenetic regulation of adipocyte differentiation and adipogenesis. J Zhejiang Univ Sci B 2010;11:784-91. https://doi.org/10.1631/jzus.B0900401
  32. Suk S, Kwon GT, Lee E, Jang WJ, Yang H, Kim JH, Thimmegowda NR, Chung MY, Kwon JY, Yang S, Kim JK, Park JH, Lee KW. Gingerenone A, a polyphenol present in ginger, suppresses obesity and adipose tissue inflammation in high-fat diet-fed mice. Mol Nutr Food Res 2017;61:1700139. https://doi.org/10.1002/mnfr.201700139
  33. Tzeng TF, Liu IM. 6-gingerol prevents adipogenesis and the accumulation of cytoplasmic lipid droplets in 3T3-L1 cells. Phytomedicine 2013;20:481-7. https://doi.org/10.1016/j.phymed.2012.12.006
  34. Tzeng TF, Chang CJ, Liu IM. 6-gingerol inhibits rosiglitazone-induced adipogenesis in 3T3-L1 adipocytes. Phytother Res 2014;28:187-92. https://doi.org/10.1002/ptr.4976
  35. Li C, Zhou L. Inhibitory effect 6-gingerol on adipogenesis through activation of the Wnt/β-catenin signaling pathway in 3T3-L1 adipocytes. Toxicol In Vitro 2015;30:394-401. https://doi.org/10.1016/j.tiv.2015.09.023
  36. Suk S, Seo SG, Yu JG, Yang H, Jeong E, Jang YJ, Yaghmoor SS, Ahmed Y, Yousef JM, Abualnaja KO, Al-Malki AL, Kumosani TA, Lee CY, Lee HJ, Lee KW. A bioactive constituent of ginger, 6-shogaol, prevents adipogenesis and stimulates lipolysis in 3T3-L1 adipocytes. J Food Biochem 2016;40:84-90. https://doi.org/10.1111/jfbc.12191
  37. Wei CK, Tsai YH, Korinek M, Hung PH, El-Shazly M, Cheng YB, Wu YC, Hsieh TJ, Chang FR. 6-paradol and 6-shogaol, the pungent compounds of ginger, promote glucose utilization in adipocytes and myotubes, and 6-paradol reduces blood glucose in high-fat diet-fed mice. Int J Mol Sci 2017;18:18. https://doi.org/10.3390/ijms18010018
  38. Ahn EK, Oh JS. Inhibitory effect of galanolactone isolated from Zingiber officinale Roscoe extract on adipogenesis in 3T3-L1 cells. J Korean Soc Appl Biol Chem 2012;55:63-8. https://doi.org/10.1007/s13765-012-0011-6
  39. Kuri-Harcuch W, Velez-delValle C, Vazquez-Sandoval A, Hernandez-Mosqueira C, Fernandez-Sanchez V. A cellular perspective of adipogenesis transcriptional regulation. J Cell Physiol 2019;234:1111-29. https://doi.org/10.1002/jcp.27060
  40. Ntambi JM, Young-Cheul K. Adipocyte differentiation and gene expression. J Nutr 2000;130:3122S-3126S.
  41. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab 2006;4:263-73. https://doi.org/10.1016/j.cmet.2006.07.001
  42. Lee JE, Ge K. Transcriptional and epigenetic regulation of PPARγ expression during adipogenesis. Cell Biosci 2014;4:29. https://doi.org/10.1186/2045-3701-4-29
  43. Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep 2001;2:282-6. https://doi.org/10.1093/embo-reports/kve071
  44. Semwal RB, Semwal DK, Combrinck S, Viljoen AM. Gingerols and shogaols: important nutraceutical principles from ginger. Phytochemistry 2015;117:554-68. https://doi.org/10.1016/j.phytochem.2015.07.012
  45. Misawa K, Hashizume K, Yamamoto M, Minegishi Y, Hase T, Shimotoyodome A. Ginger extract prevents high-fat diet-induced obesity in mice via activation of the peroxisome proliferator-activated receptor δ pathway. J Nutr Biochem 2015;26:1058-67. https://doi.org/10.1016/j.jnutbio.2015.04.014
  46. Fuhrman B, Rosenblat M, Hayek T, Coleman R, Aviram M. Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice. J Nutr 2000;130:1124-31. https://doi.org/10.1093/jn/130.5.1124
  47. Goyal RK, Kadnur SV. Beneficial effects of Zingiber officinale on goldthioglucose induced obesity. Fitoterapia 2006;77:160-3. https://doi.org/10.1016/j.fitote.2006.01.005
  48. Nammi S, Sreemantula S, Roufogalis BD. Protective effects of ethanolic extract of Zingiber officinale rhizome on the development of metabolic syndrome in high-fat diet-fed rats. Basic Clin Pharmacol Toxicol 2009;104:366-73. https://doi.org/10.1111/j.1742-7843.2008.00362.x
  49. Li Y, Tran VH, Kota BP, Nammi S, Duke CC, Roufogalis BD. Preventative effect of Zingiber officinale on insulin resistance in a high-fat high-carbohydrate diet-fed rat model and its mechanism of action. Basic Clin Pharmacol Toxicol 2014;115:209-15. https://doi.org/10.1111/bcpt.12196
  50. Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol 2005;97:227-30. https://doi.org/10.1016/j.jep.2004.11.011
  51. Bhandari U, Sharma JN, Zafar R. The protective action of ethanolic ginger (Zingiber officinale) extract in cholesterol fed rabbits. J Ethnopharmacol 1998;61:167-71. https://doi.org/10.1016/S0378-8741(98)00026-9
  52. ElRokh SM, Yassin NA, El-Shenawy SM, Ibrahim BM. Antihypercholesterolaemic effect of ginger rhizome (Zingiber officinale) in rats. Inflammopharmacology 2010;18:309-15. https://doi.org/10.1007/s10787-010-0053-5
  53. Matsuda A, Wang Z, Takahashi S, Tokuda T, Miura N, Hasegawa J. Upregulation of mRNA of retinoid binding protein and fatty acid binding protein by cholesterol enriched-diet and effect of ginger on lipid metabolism. Life Sci 2009;84:903-7. https://doi.org/10.1016/j.lfs.2009.04.004
  54. Beattie JH, Nicol F, Gordon MJ, Reid MD, Cantlay L, Horgan GW, Kwun IS, Ahn JY, Ha TY. Ginger phytochemicals mitigate the obesogenic effects of a high-fat diet in mice: a proteomic and biomarker network analysis. Mol Nutr Food Res 2011;55 Suppl 2:S203-13. https://doi.org/10.1002/mnfr.201100193
  55. Son MJ, Miura Y, Yagasaki K. Mechanisms for antidiabetic effect of gingerol in cultured cells and obese diabetic model mice. Cytotechnology 2015;67:641-52. https://doi.org/10.1007/s10616-014-9730-3
  56. Saravanan G, Ponmurugan P, Deepa MA, Senthilkumar B. Anti-obesity action of gingerol: effect on lipid profile, insulin, leptin, amylase and lipase in male obese rats induced by a high-fat diet. J Sci Food Agric 2014;94:2972-7. https://doi.org/10.1002/jsfa.6642
  57. Tzeng TF, Liou SS, Chang CJ, Liu IM. [6]-gingerol dampens hepatic steatosis and inflammation in experimental nonalcoholic steatohepatitis. Phytomedicine 2015;22:452-61. https://doi.org/10.1016/j.phymed.2015.01.015
  58. Lei L, Liu Y, Wang X, Jiao R, Ma KY, Li YM, Wang L, Man SW, Sang S, Huang Y, Chen ZY. Plasma cholesterol-lowering activity of gingerol- and shogaol-enriched extract is mediated by increasing sterol excretion. J Agric Food Chem 2014;62:10515-21. https://doi.org/10.1021/jf5043344
  59. Wang J, Gao H, Ke D, Zuo G, Yang Y, Yamahara J, Li Y. Improvement of liquid fructose-induced adipose tissue insulin resistance by ginger treatment in rats is associated with suppression of adipose macrophage-related proinflammatory cytokines. Evid Based Complement Alternat Med 2013;2013:590376.
  60. de Las Heras N, Valero-Munoz M, Martin-Fernandez B, Ballesteros S, Lopez-Farre A, Ruiz-Roso B, Lahera V. Molecular factors involved in the hypolipidemic- and insulin-sensitizing effects of a ginger (Zingiber officinale Roscoe) extract in rats fed a high-fat diet. Appl Physiol Nutr Metab 2017;42:209-15. https://doi.org/10.1139/apnm-2016-0374
  61. Al-Amin ZM, Thomson M, Al-Qattan KK, Peltonen-Shalaby R, Ali M. Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats. Br J Nutr 2006;96:660-6. https://doi.org/10.1079/bjn20061849
  62. Abdulrazaq NB, Cho MM, Win NN, Zaman R, Rahman MT. Beneficial effects of ginger (Zingiber officinale) on carbohydrate metabolism in streptozotocin-induced diabetic rats. Br J Nutr 2012;108:1194-201. https://doi.org/10.1017/S0007114511006635
  63. Jafri SA, Abass S, Qasim M. Hypoglycemic effect of ginger (Zingiber officinale) in alloxan induced diabetic rats (Rattus norvagicus). Pak Vet J 2011;31:160-2.
  64. Wang QA, Tao C, Gupta RK, Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 2013;19:1338-44. https://doi.org/10.1038/nm.3324
  65. Kim S, Lee MS, Jung S, Son HY, Park S, Kang B, Kim SY, Kim IH, Kim CT, Kim Y. Ginger extract ameliorates obesity and inflammation via regulating microRNA-21/132 expression and AMPK activation in white adipose tissue. Nutrients 2018;10:10. https://doi.org/10.3390/nu10010010
  66. Fruhbeck G, Mendez-Gimenez L, Fernandez-Formoso JA, Fernandez S, Rodriguez A. Regulation of adipocyte lipolysis. Nutr Res Rev 2014;27:63-93. https://doi.org/10.1017/S095442241400002X
  67. Wang H, Eckel RH. Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab 2009;297:E271-88. https://doi.org/10.1152/ajpendo.90920.2008
  68. Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, Lass A, Madeo F. FAT SIGNALS- -lipases and lipolysis in lipid metabolism and signaling. Cell Metab 2012;15:279-91. https://doi.org/10.1016/j.cmet.2011.12.018

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