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Green tea beneficial effects involve changes in the profile of immune cells in the adipose tissue of obese mice

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Abstract

Purpose

During obesity, the adipose tissue is usually infiltrated by immune cells which are related to hallmarks of obesity such as systemic inflammation and insulin resistance (IR). Green tea (GT) has been widely studied for its anti-inflammatory actions, including the modulation in the proliferation and activity of immune cells, in addition to preventing cardiovascular and metabolic diseases.

Methods

The aim of the present study was to analyze the population of immune cells present in the subcutaneous and epididymal white adipose tissue (WAT) of mice kept at thermoneutrality (TN) and fed with a high-fat diet (HFD) for 16 weeks, supplemented or not with GT extract (500 mg/kg/12 weeks).

Results

The HFD in association with TN has induced chronic inflammation, and IR in parallel with changes in the profile of immune cells in the subcutaneous and epidydimal WAT, increasing pro-inflammatory cytokines release, inflammatory cells infiltration, and fibrotic aspects in WAT. On the other hand, GT prevented body weight gain, in addition to avoiding IR and inflammation, and the consequent tissue fibrosis, maintaining a lower concentration of cytokines and a profile of immune cells similar to the control mice, preventing the harmful modulations induced by both HFD and TN.

Conclusions

GT beneficial effects in WAT abrogated the deleterious effects triggered by HFD and TN, maintaining all immune cells and fibrotic markers at the same level as in lean mice. These results place WAT immune cells population as a potential target of GT action, also highlighting the positive effects of GT in obese mice housed at TN.

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References

  1. Kim J, Nam JH (2020) Insight into the relationship between obesity-induced low-level chronic inflammation and COVID-19 infection. Int J Obes 44:1541–1542. https://doi.org/10.1038/s41366-020-0602-y

    Article  CAS  Google Scholar 

  2. Longo M, Zatterale F, Naderi J et al (2019) Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int J Mol Sci. https://doi.org/10.3390/ijms20092358

    Article  Google Scholar 

  3. Blüher M (2019) Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. https://doi.org/10.1038/s41574-019-0176-8

    Article  Google Scholar 

  4. Rosen ED, Spiegelman BM (2014) What we talk about when we talk about fat. Cell 156:20–44. https://doi.org/10.1016/j.cell.2013.12.012

    Article  CAS  Google Scholar 

  5. Kane H, Lynch L (2019) Innate immune control of adipose tissue homeostasis. Trends Immunol 40:857–872. https://doi.org/10.1016/j.it.2019.07.006

    Article  CAS  Google Scholar 

  6. Huh JY, Park YJ, Ham M, Kim JB (2014) Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol Cells 37:365–371. https://doi.org/10.14348/molcells.2014.0074

    Article  CAS  Google Scholar 

  7. Vieira-Potter VJ (2014) Inflammation and macrophage modulation in adipose tissues. Cell Microbiol 16:1484–1492. https://doi.org/10.1111/cmi.12336

    Article  CAS  Google Scholar 

  8. Davanzo GG, Castro G, Moraes-Vieira PMM (2021) Immunometabolic regulation of adipose tissue resident immune cells. Curr Opin Pharmacol 58:44–51. https://doi.org/10.1016/J.COPH.2021.03.004

    Article  CAS  Google Scholar 

  9. Hotamisligil GS, Spiegelman BM (1994) Perspectives in diabetes tumor necrosis factor a: a key component of the obesity-diabetes link. Diabetes 43:1271–1278

    Article  CAS  Google Scholar 

  10. Henninger AJ, Eliasson B, Jenndahl LE, Hammarstedt A (2014) Adipocyte hypertrophy, inflammation and fibrosis characterize subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes. PLoS One. https://doi.org/10.1371/JOURNAL.PONE.0105262

    Article  Google Scholar 

  11. Sun K, Kusminski CM, Scherer P (2011) Adipose tissue remodeling and obesity. J Clin Investig. https://doi.org/10.1172/JCI45887.2094

    Article  Google Scholar 

  12. Ellulu MS, Patimah I, Khaza H et al (2017) Obesity and inflammation: the linking mechanism and the complications. Archives Med Sci. https://doi.org/10.5114/aoms.2016.58928

    Article  Google Scholar 

  13. Catrysse L, van Loo G (2018) Adipose tissue macrophages and their polarization in health and obesity. Cell Immunol 330:114–119. https://doi.org/10.1016/j.cellimm.2018.03.001

    Article  CAS  Google Scholar 

  14. Rotter V, Nagaev I, Smith U (2003) Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and Tumor necrosis factor-α, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 278:45777–45784. https://doi.org/10.1074/jbc.M301977200

    Article  CAS  Google Scholar 

  15. Wensveen FM, Valentić S, Šestan M et al (2015) Interactions between adipose tissue and the immune system in health and malnutrition. Semin Immunol 27:322–333. https://doi.org/10.1016/j.smim.2015.10.006

    Article  CAS  Google Scholar 

  16. Daniele G, Guardado Mendoza R, Winnier D et al (2014) The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol 51:123–131. https://doi.org/10.1007/S00592-013-0543-1

    Article  CAS  Google Scholar 

  17. Flehmig G, Scholz M, Klöting N et al (2014) Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation. PLoS One 9:e99785. https://doi.org/10.1371/JOURNAL.PONE.0099785

    Article  Google Scholar 

  18. Braune J, Weyer U, Hobusch C et al (2017) IL-6 regulates M2 polarization and local proliferation of adipose tissue macrophages in obesity. J Immunol 198:2927–2934. https://doi.org/10.4049/JIMMUNOL.1600476

    Article  CAS  Google Scholar 

  19. Hwang I, Kim JB (2019) Two faces of white adipose tissue with heterogeneous adipogenic progenitors. Diabetes Metab J 43:752. https://doi.org/10.4093/dmj.2019.0174

    Article  Google Scholar 

  20. Villarroya F, Cereijo R, Villarroya J et al (2018) Toward an understanding of how immune cells control brown and beige adipobiology. Cell Metab 27:954–961. https://doi.org/10.1016/j.cmet.2018.04.006

    Article  CAS  Google Scholar 

  21. Cox AR, Chernis N, Masschelin PM, Hartig SM (2019) Immune cells gate white adipose tissue expansion. Endocrinology 160:1645–1658. https://doi.org/10.1210/en.2019-00266

    Article  CAS  Google Scholar 

  22. Misumi I, Starmer J, Uchimura T et al (2019) Obesity expands a distinct population of T cells in adipose tissue and increases vulnerability to infection. Cell Rep 27:514-524.e5. https://doi.org/10.1016/j.celrep.2019.03.030

    Article  CAS  Google Scholar 

  23. Dosch H-M, Engleman E, Zielenski J et al (2009) Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 15:921–929. https://doi.org/10.1038/nm.2001

    Article  CAS  Google Scholar 

  24. Francisco V, Pino J, Campos-Cabaleiro V et al (2018) Obesity, fat mass and immune system: role for leptin. Front Physiol 9:640. https://doi.org/10.3389/fphys.2018.00640

    Article  Google Scholar 

  25. Otton R, Bolin AP, Ferreira LT et al (2018) Polyphenol-rich green tea extract improves adipose tissue metabolism by down-regulating miR-335 expression and mitigating insulin resistance and inflammation. J Nutr Biochem 57:170–179. https://doi.org/10.1016/J.JNUTBIO.2018.03.024

    Article  CAS  Google Scholar 

  26. Bolin AP, Sousa-Filho CPB, dos Santos GTN et al (2020) Adipogenic commitment induced by green tea polyphenols remodel adipocytes to a thermogenic phenotype. J Nutr Biochem. https://doi.org/10.1016/J.JNUTBIO.2020.108429

    Article  Google Scholar 

  27. Sousa-Filho CPB, Faria HOF, Esposito JC et al (2020) Green tea improves the metabolism of peripheral tissues in β3-adrenergic receptor-knockout mice. Pharmacol Res. https://doi.org/10.1016/J.PHRS.2020.104956

    Article  Google Scholar 

  28. Xing L, Zhang H, Qi R et al (2019) Recent advances in the understanding of the health benefits and molecular mechanisms associated with green tea polyphenols. J Agric Food Chem 67:1029–1043. https://doi.org/10.1021/ACS.JAFC.8B06146

    Article  CAS  Google Scholar 

  29. Tang GY, Meng X, Gan RY et al (2019) Health functions and related molecular mechanisms of tea components: an update review. Int J Mol Sci 20(24):6196

    Article  CAS  Google Scholar 

  30. Otton R, Bolin AP, Ferreira LT et al (2018) Polyphenol-rich green tea extract improves adipose tissue metabolism by down-regulating miR-335 expression and mitigating insulin resistance and inflammation. J Nutr Biochem. https://doi.org/10.1016/j.jnutbio.2018.03.024

    Article  Google Scholar 

  31. Bolin AP, Sousa-Filho CPB, Marinovic MP et al (2020) Polyphenol-rich green tea extract induces thermogenesis in mice by a mechanism dependent on adiponectin signaling. J Nutr Biochem. https://doi.org/10.1016/J.JNUTBIO.2019.108322

    Article  Google Scholar 

  32. Lang P, Hasselwander S, Li H (2019) Xia N (2019) Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL/6 mice. Sci Reports 91(9):1–14. https://doi.org/10.1038/s41598-019-55987-x

    Article  CAS  Google Scholar 

  33. Clayton ZS, McCurdy CE (2018) Short-term thermoneutral housing alters glucose metabolism and markers of adipose tissue browning in response to a high-fat diet in lean mice. Am J Physiol 315:R627–R637. https://doi.org/10.1152/AJPREGU.00364.2017

    Article  CAS  Google Scholar 

  34. Fischer AW, Cannon B, Nedergaard J (2019) The answer to the question “What is the best housing temperature to translate mouse experiments to humans?” is: thermoneutrality. Mol Metab 26:1–3

    Article  CAS  Google Scholar 

  35. Keijer J, Li M, Speakman JR (2019) What is the best housing temperature to translate mouse experiments to humans? Mol Metab 25:168–176. https://doi.org/10.1016/j.molmet.2019.04.001

    Article  CAS  Google Scholar 

  36. Neff EP (2020) A point on thermoneutrality for mice. Lab Anim (NY) 49:169. https://doi.org/10.1038/s41684-020-0560-y

    Article  Google Scholar 

  37. Stemmer K, Kotzbeck P, Zani F et al (2015) Thermoneutral housing is a critical factor for immune function and diet-induced obesity in C57BL/6 nude mice. Int J Obes 39:791–797. https://doi.org/10.1038/ijo.2014.187

    Article  CAS  Google Scholar 

  38. Fischer AW, de Jong JMA, Sass F et al (2020) Thermoneutrality-induced macrophage accumulation in brown adipose tissue does not impair the tissue’s competence for cold-induced thermogenic recruitment. Front Endocrinol (Lausanne) 11:1–17. https://doi.org/10.3389/fendo.2020.568682

    Article  Google Scholar 

  39. Vialard F, Olivier M (2020) Thermoneutrality and immunity: how does cold stress affect disease? Front Immunol 11:3–7. https://doi.org/10.3389/fimmu.2020.588387

    Article  CAS  Google Scholar 

  40. Djeridane A, Yousfi M, Nadjemi B et al (2006) Antioxidant activity of some algerian medicinal plants extracts containing phenolic compounds. Food Chem 97:654–660. https://doi.org/10.1016/J.FOODCHEM.2005.04.028

    Article  CAS  Google Scholar 

  41. Kwon EY, Jung UJ, Park T et al (2015) Luteolin attenuates hepatic steatosis and insulin resistance through the interplay between the liver and adipose tissue in mice with diet-induced obesity. Diabetes 64:1658–1669. https://doi.org/10.2337/DB14-0631

    Article  CAS  Google Scholar 

  42. Zhi X, Wang J, Lu P et al (2018) AdipoCount: a new software for automatic adipocyte counting. Front Physiol 9:1–9. https://doi.org/10.3389/fphys.2018.00085

    Article  Google Scholar 

  43. Junqueira LCU, Bignolas G, Brentani RR (1979) Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J 11:447–455. https://doi.org/10.1007/BF01002772

    Article  CAS  Google Scholar 

  44. Dulloo AG, Duret C, Rohrer D et al (1999) Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr 70:1040–1045. https://doi.org/10.1093/AJCN/70.6.1040

    Article  CAS  Google Scholar 

  45. Yang CS, Hong J (2013) Prevention of chronic diseases by tea: possible mechanisms and human relevance. Annu Rev Nutr 33:161–181. https://doi.org/10.1146/ANNUREV-NUTR-071811-150717

    Article  CAS  Google Scholar 

  46. Yang W, Tian Z, Wu Y et al (2016) Innate lymphoid cells as novel regulators of obesity and its-associated metabolic dysfunction. Obes Rev 17:485–498. https://doi.org/10.1111/obr.12397

    Article  CAS  Google Scholar 

  47. Huang J, Wang Y, Xie Z et al (2014) The anti-obesity effects of green tea in human intervention and basic molecular studies. Eur J Clin Nutr 68:1075–1087. https://doi.org/10.1038/ejcn.2014.143

    Article  CAS  Google Scholar 

  48. Wang S, Moustaid-Moussa N, Chen L et al (2014) Novel insights of dietary polyphenols and obesity. J Nutr Biochem 25:1–18. https://doi.org/10.1016/j.jnutbio.2013.09.001

    Article  CAS  Google Scholar 

  49. Hursel R, Westerterp-Plantenga MS (2013) Catechin- and caffeine-rich teas for control of body weight in humans. Am J Clin Nutr. https://doi.org/10.3945/AJCN.113.058396

    Article  Google Scholar 

  50. Chen D, Wang CY, Lambert JD et al (2005) Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies. Biochem Pharmacol 69:1523–1531. https://doi.org/10.1016/J.BCP.2005.01.024

    Article  CAS  Google Scholar 

  51. Yang CS, Zhang J, Zhang L et al (2016) Mechanisms of body weight reduction and metabolic syndrome alleviation by tea. Mol Nutr Food Res 60:160–174. https://doi.org/10.1002/MNFR.201500428

    Article  CAS  Google Scholar 

  52. Haghighatdoost F, Gh BFNM, Hariri M (2017) Effect of green tea on plasma adiponectin levels: a systematic review and meta-analysis of randomized controlled clinical trials. J Am Coll Nutr 36:541–548. https://doi.org/10.1080/07315724.2017.1333470

    Article  CAS  Google Scholar 

  53. Dulloo AG, Seydoux J, Girardier L (1992) Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition? Metabolism 41:1233–1241. https://doi.org/10.1016/0026-0495(92)90015-3

    Article  CAS  Google Scholar 

  54. Singer K, Lumeng CN (2017) The initiation of metabolic inflammation in childhood obesity. J Clin Invest 127:65–73. https://doi.org/10.1172/JCI88882

    Article  Google Scholar 

  55. Fischer AW, de Jong JMA, Sass F et al (2020) Thermoneutrality-induced macrophage accumulation in brown adipose tissue does not impair the tissue’s competence for cold-induced thermogenic recruitment. Front Endocrinol (Lausanne) 11:804. https://doi.org/10.3389/fendo.2020.568682

    Article  Google Scholar 

  56. Russo L, Lumeng CN (2018) Properties and functions of adipose tissue macrophages in obesity. Immunology 155:407–417. https://doi.org/10.1111/IMM.13002

    Article  CAS  Google Scholar 

  57. Zheng C, Yang Q, Cao J et al (2016) Local proliferation initiates macrophage accumulation in adipose tissue during obesity. Cell Death Dis 73(7):e2167–e2167. https://doi.org/10.1038/cddis.2016.54

    Article  CAS  Google Scholar 

  58. Samanta S (2020) Potential bioactive components and health promotional benefits of tea (Camellia sinensis). J Am Coll Nutr. https://doi.org/10.1080/07315724.2020.1827082

    Article  Google Scholar 

  59. Konstantinidi M, Koutelidakis AE (2019) Functional foods and bioactive compounds: a review of its possible role on weight management and obesity’s metabolic consequence. Medicine 6:94. https://doi.org/10.3390/MEDICINES6030094

    Article  CAS  Google Scholar 

  60. Rocha A, Bolin AP, Cardoso CAL, Otton R (2016) Green tea extract activates AMPK and ameliorates white adipose tissue metabolic dysfunction induced by obesity. Eur J Nutr 55:2231–2244. https://doi.org/10.1007/s00394-015-1033-8

    Article  CAS  Google Scholar 

  61. Torres LF, Cogliati B, Otton R (2019) Green tea prevents NAFLD by modulation of miR-34a and miR-194 expression in a high-fat diet mouse model. Oxid Med Cell Longev. https://doi.org/10.1155/2019/4168380

    Article  Google Scholar 

  62. VojtechSkop A, Guo J, Liu N et al (2020) Mouse thermoregulation: introducing the concept of the thermoneutral point. Cell Report. https://doi.org/10.1016/j.celrep.2020.03.065

    Article  Google Scholar 

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Acknowledgements

The authors are indebted to the assistance of Dr. Alexandre Steiner and Dr. Eduardo H. Moretti, for indirect calorimeter machine utilization and support, and to all Otton’s Lab members for helping in mice care. The authors are grateful to Alembert Eistein Lino Alvarado for technical assistance in picrosirius staining analyses. This research was supported by the São Paulo Research Foundation (FAPESP, process no. 2019/10616-5), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)—Finance Code 001 and Cruzeiro do Sul University.

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Authors and Affiliations

  1. Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, Regente Feijó Avenue, 1295, Sao Paulo, SP, 03342-000, Brazil

    Kaue Tognolli, Victoria Silva, Celso Pereira Batista Sousa-Filho, Renata Gorjão & Rosemari Otton

  2. Mato Grosso do Sul State University, Dourados, MS, Brazil

    Claudia Andrea Lima Cardoso

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  1. Kaue Tognolli
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Tognolli, K., Silva, V., Sousa-Filho, C.P.B. et al. Green tea beneficial effects involve changes in the profile of immune cells in the adipose tissue of obese mice. Eur J Nutr 62, 321–336 (2023). https://doi.org/10.1007/s00394-022-02963-3

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