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Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention

Abstract

Purpose

Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. Obesity stimulates cancer progression through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular, the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter ATM phenotype in obese postmenopausal breast cancer survivors.

Methods

Twenty obese postmenopausal breast cancer survivors were randomized to a 16-week aerobic and resistance exercise (EX) intervention or delayed intervention control (CON). The EX group participated in 16 weeks of supervised exercise sessions 3 times/week. Participants provided fasting blood, dual-energy X-ray absorptiometry (DXA), and superficial subcutaneous abdominal adipose tissue biopsies at baseline and following the 16-week study period.

Results

EX participants experienced significant improvements in body composition, cardiometabolic biomarkers, and systemic inflammation (all p < 0.03 vs. CON). Adipose tissue from EX participants showed a significant decrease in ATM M1 (p < 0.001), an increase in ATM M2 (p < 0.001), increased adipose tissue secretion of anti-inflammatory cytokines such as adiponectin, and decreased secretion of the pro-inflammatory cytokines IL-6 and TNF- α (all p < 0.055).

Conclusions

A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence.

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References

  1. 1.

    Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29

    Article  PubMed  Google Scholar 

  2. 2.

    Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123(3):627–635

    Article  PubMed  Google Scholar 

  3. 3.

    Iyengar NM, Hudis CA, Dannenberg AJ (2013) Obesity and inflammation: new insights into breast cancer development and progression. American Society of Clinical Oncology educational book/ASCO American Society of Clinical Oncology Meeting:46–51

  4. 4.

    Campbell KL, Makar KW, Kratz M, Foster-Schubert KE, McTiernan A, Ulrich CM (2009) A pilot study of sampling subcutaneous adipose tissue to examine biomarkers of cancer risk. Cancer Prev Res (Phila) 2(1):37–42

    CAS  Article  Google Scholar 

  5. 5.

    Campbell KL, Foster-Schubert KE, Makar KW, Kratz M, Hagman D, Schur EA et al (2013) Gene expression changes in adipose tissue with diet- and/or exercise-induced weight loss. Cancer Prev Res (Phila) 6(3):217–231

    CAS  Article  Google Scholar 

  6. 6.

    Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3(1):23–35

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5(12):953–964

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Fujisaka S, Usui I, Bukhari A, Ikutani M, Oya T, Kanatani Y et al (2009) Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58(11):2574–2582

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Cao Y (2010) Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev Drug Discov 9(2):107–115

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Mayi TH, Daoudi M, Derudas B, Gross B, Bories G, Wouters K et al (2012) Human adipose tissue macrophages display activation of cancer-related pathways. J Biol Chem 287(26):21904–21913

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454(7203):436–444

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Auerbach P, Nordby P, Bendtsen LQ, Mehlsen JL, Basnet SK, Vestergaard H et al (2013) Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men. Am J Physiol Regul Integr Comp Physiol 305(5):R490–R498

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Ahmadizad S, Ghorbani S, Ghasemikaram M, Bahmanzadeh M (2014) Effects of short-term nonperiodized, linear periodized and daily undulating periodized resistance training on plasma adiponectin, leptin and insulin resistance. Clin Biochem 47(6):417–422

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Kang DW, Lee J, Suh SH, Ligibel J, Courneya KS, Jeon JY (2017) Effects of exercise on insulin, igf axis, adipocytokines, and inflammatory markers in breast cancer survivors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 26(3):355–365

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Meneses-Echavez JF, Correa-Bautista JE, Gonzalez-Jimenez E, Schmidt Rio-Valle J, Elkins MR, Lobelo F et al (2016) The effect of exercise training on mediators of inflammation in breast cancer survivors: a systematic review with meta-analysis. Cancer Epidemiol Biomarkers Prev 25(7):1009–1017

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Ebbeling CB, Ward A, Puleo EM, Widrick J, Rippe JM (1991) Development of a single-stage submaximal treadmill walking test. Med Sci Sports Exerc 23(8):966–973

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Brzycki M (1993) Strength testing: predicting a one-rep max from repetition-to-fatigue. JOHPERD 64:88–90

    Google Scholar 

  18. 18.

    Rock CL, Doyle C, Demark-Wahnefried W, Meyerhardt J, Courneya KS, Schwartz AL et al (2012) Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 62(4):243–274

    Article  PubMed  Google Scholar 

  19. 19.

    Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM et al (2010) American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 42(7):1409–1426

    Article  PubMed  Google Scholar 

  20. 20.

    Alderete TL, Sattler FR, Richey JM, Allayee H, Mittelman SD, Sheng X et al (2015) Salsalate treatment improves glycemia without altering adipose tissue in nondiabetic obese hispanics. Obesity (Silver Spring) 23(3):543–551

    CAS  Article  Google Scholar 

  21. 21.

    Oliveira AG, Araujo TG, Carvalho BM, Guadagnini D, Rocha GZ, Bagarolli RA et al (2013) Acute exercise induces a phenotypic switch in adipose tissue macrophage polarization in diet-induced obese rats. Obesity 21(12):2545–2556

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Kawanishi N, Yano H, Yokogawa Y, Suzuki K (2010) Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exerc Immunol Rev 16:105–118

    PubMed  Google Scholar 

  23. 23.

    Linden MA, Pincu Y, Martin SA, Woods JA, Baynard T (2014) Moderate exercise training provides modest protection against adipose tissue inflammatory gene expression in response to high-fat feeding. Physiol Rep 2(7):e12071

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Rogers LQ, Fogleman A, Trammell R, Hopkins-Price P, Vicari S, Rao K et al (2013) Effects of a physical activity behavior change intervention on inflammation and related health outcomes in breast cancer survivors: pilot randomized trial. Integr Cancer Ther 12(4):323–335

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Ergun M, Eyigor S, Karaca B, Kisim A, Uslu R (2013) Effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in breast cancer patients. Eur J Cancer Care (Engl) 22(5):626–637

    CAS  Article  Google Scholar 

  26. 26.

    Hutnick NA, Williams NI, Kraemer WJ, Orsega-Smith E, Dixon RH, Bleznak AD et al (2005) Exercise and lymphocyte activation following chemotherapy for breast cancer. Med Sci Sports Exerc 37(11):1827–1835

    Article  PubMed  Google Scholar 

  27. 27.

    Gomez AM, Martinez C, Fiuza-Luces C, Herrero F, Perez M, Madero L et al (2011) Exercise training and cytokines in breast cancer survivors. Int J Sports Med 32(6):461–467

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y et al (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20(1):42–51

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL et al (2008) Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 300(23):2754–2764

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK et al (2009) American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc 41(2):459–471

    Article  PubMed  Google Scholar 

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Acknowledgements

We are grateful to the Clinical Investigations Support Office of the Norris Comprehensive Cancer Center for their support of this investigation and the extreme generosity of our study participants. This work was supported by grants K07CA160718 from the National Cancer Institute; and grants UL1TR001855 and UL1TR000130 from the National Center for Advancing Translational Science (NCATS) of the U.S. National Institutes of Health. The content is solely the responsibility of the authors, and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to Christina M. Dieli-Conwright.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Dieli-Conwright, C.M., Parmentier, JH., Sami, N. et al. Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention. Breast Cancer Res Treat 168, 147–157 (2018). https://doi.org/10.1007/s10549-017-4576-y

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Keywords

  • Adipose tissue
  • Macrophages
  • Obesity
  • Body composition