Plasma Cytokine Levels in Overweight Versus Obese Disease-Free Perimenopausal Women

Author(s): Anna C.B.N. Maniçoba, Leonardo V. Galvão-Moreira, Izabella M.S.C. D'Albuquerque, Haissa O. Brito, Johnny R. do Nascimento, Flávia R.F. do Nascimento, Maria do C.L. Barbosa, Rui M.G. da Costa, Maria do D.S.B. Nascimento, Manuel dos S. Faria, Luciane M.O. Brito*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 20 , Issue 6 , 2020

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Graphical Abstract:


Abstract:

Objective: To evaluate the plasma cytokine levels during T cell-mediated inflammatory responses and compare the metabolic markers between overweight and obese perimenopausal women without systemic diseases.

Methods: Sixty perimenopausal women were divided into two groups (overweight and obese). Participants in both groups had their waist-to-height ratio (WHtR) measured and blood samples collected for the evaluation of estradiol, fasting glucose, leptin, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-10, IL-17A levels, and lipid profile.

Results: In univariate analysis, women with obesity showed increased WHtR, fasting glucose, leptin, and IL-6 (p < 0.05) levels; however, significant differences were not observed in IL-10 or IL-17A (p > 0.05) levels. In the receiver operating characteristic curve, the highest areas under the curve were shown for leptin (0.856) and IL-6 (0.706). IL-6 levels correlated with both hs-CRP (r = 0.302, p = 0.020) and leptin (r = 0.294, p = 0.022). However, in multivariate analysis, IL-6 was not associated with a greater likelihood of obesity (OR = 1.61; 95% CI: 0.82-3.15; p = 0.16), when potential confounders were considered.

Conclusion: IL-6 levels varied between overweight and obese perimenopausal women, and this association was weaker when adjusted for other clinical variables.

Keywords: Menopause, obesity, inflammation, biomarkers, cytokines, leptin.

[1]
Henstridge, D.C.; Abildgaard, J.; Lindegaard, B.; Febbraio, M.A. Metabolic control and sex: A focus on inflammatory-linked mediators. Br. J. Pharmacol., 2019, 176(21), 4193-4207.
[http://dx.doi.org/10.1111/bph.14642] [PMID: 30820935]
[2]
Colpani, V.; Baena, C.P.; Jaspers, L.; van Dijk, G.M.; Farajzadegan, Z.; Dhana, K.; Tielemans, M.J.; Voortman, T.; Freak-Poli, R.; Veloso, G.G.V.; Chowdhury, R.; Kavousi, M.; Muka, T.; Franco, O.H. Lifestyle factors, cardiovascular disease and all-cause mortality in middle-aged and elderly women: a systematic review and meta-analysis. Eur. J. Epidemiol., 2018, 33(9), 831-845.
[http://dx.doi.org/10.1007/s10654-018-0374-z] [PMID: 29524110]
[3]
Namazi, N.; Irandoost, P.; Heshmati, J.; Larijani, B.; Azadbakht, L. The association between fat mass and the risk of breast cancer: A systematic review and meta-analysis. Clin. Nutr., 2019, 38(4), 1496-1503.
[http://dx.doi.org/10.1016/j.clnu.2018.09.013] [PMID: 30305235]
[4]
Wang, T.; Rohan, T.E.; Gunter, M.J.; Xue, X.; Wactawski-Wende, J.; Rajpathak, S.N.; Cushman, M.; Strickler, H.D.; Kaplan, R.C.; Wassertheil-Smoller, S.; Scherer, P.E.; Ho, G.Y. A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers. Cancer Epidemiol. Biomarkers Prev., 2011, 20(5), 971-977.
[http://dx.doi.org/10.1158/1055-9965.EPI-10-1222] [PMID: 21415362]
[5]
Nimptsch, K.; Konigorski, S.; Pischon, T. Diagnosis of obesity and use of obesity biomarkers in science and clinical medicine. Metabolism, 2019, 92, 61-70.
[http://dx.doi.org/10.1016/j.metabol.2018.12.006] [PMID: 30586573]
[6]
You, T.; Berman, D.M.; Ryan, A.S.; Nicklas, B.J. Effects of hypocaloric diet and exercise training on inflammation and adipocyte lipolysis in obese postmenopausal women. J. Clin. Endocrinol. Metab., 2004, 89(4), 1739-1746.
[http://dx.doi.org/10.1210/jc.2003-031310] [PMID: 15070939]
[7]
Ryan, A.S.; Nicklas, B.J. Reductions in plasma cytokine levels with weight loss improve insulin sensitivity in overweight and obese postmenopausal women. Diabetes Care, 2004, 27(7), 1699-1705.
[http://dx.doi.org/10.2337/diacare.27.7.1699] [PMID: 15220249]
[8]
Arsenault, B.J.; Côté, M.; Cartier, A.; Lemieux, I.; Després, J.P.; Ross, R.; Earnest, C.P.; Blair, S.N.; Church, T.S. Effect of exercise training on cardiometabolic risk markers among sedentary, but metabolically healthy overweight or obese post-menopausal women with elevated blood pressure. Atherosclerosis, 2009, 207(2), 530-533.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.05.009] [PMID: 19524243]
[9]
Joseph, L.J.; Prigeon, R.L.; Blumenthal, J.B.; Ryan, A.S.; Goldberg, A.P. Weight loss and low-intensity exercise for the treatment of metabolic syndrome in obese postmenopausal women. J. Gerontol. A Biol. Sci. Med. Sci., 2011, 66(9), 1022-1029.
[http://dx.doi.org/10.1093/gerona/glr093] [PMID: 21653990]
[10]
Piché, M.E.; Weisnagel, S.J.; Corneau, L.; Nadeau, A.; Bergeron, J.; Lemieux, S. Contribution of abdominal visceral obesity and insulin resistance to the cardiovascular risk profile of postmenopausal women. Diabetes, 2005, 54(3), 770-777.
[http://dx.doi.org/10.2337/diabetes.54.3.770] [PMID: 15734855]
[11]
Piché, M.E.; Lemieux, S.; Weisnagel, S.J.; Corneau, L.; Nadeau, A.; Bergeron, J. Relation of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and fibrinogen to abdominal adipose tissue, blood pressure, and cholesterol and triglyceride levels in healthy postmenopausal women. Am. J. Cardiol., , 2005, 96( 1), 92-97. B.
[http://dx.doi.org/10.1016/j.amjcard.2005.02.051] [PMID: 15979442]
[12]
Blümel, J.E.; Castelo-Branco, C.; Rocangliolo, M.E.; Bifa, L.; Tacla, X.; Mamani, L. Changes in body mass index around menopause: a population study of Chilean woman. Menopause, 2001, 8(4), 239-244.
[http://dx.doi.org/10.1097/00042192-200107000-00004] [PMID: 11449080]
[13]
Khan, U.I.; Wang, D.; Karvonen-Gutierrez, C.A.; Khalil, N.; Ylitalo, K.R.; Santoro, N. Progression from metabolically benign to at-risk obesity in perimenopausal women: a longitudinal analysis of study of women across the nation (SWAN). J. Clin. Endocrinol. Metab., 2014, 99(7), 2516-2525.
[http://dx.doi.org/10.1210/jc.2013-3259] [PMID: 24846534]
[14]
Yasui, T.; Maegawa, M.; Tomita, J.; Miyatani, Y.; Yamada, M.; Uemura, H.; Matsuzaki, T.; Kuwahara, A.; Kamada, M.; Tsuchiya, N.; Yuzurihara, M.; Takeda, S.; Irahara, M. Changes in serum cytokine concentrations during the menopausal transition. Maturitas, 2007, 56(4), 396-403.
[http://dx.doi.org/10.1016/j.maturitas.2006.11.002] [PMID: 17164077]
[15]
Yasui, T.; Uemura, H.; Yamada, M.; Matsuzaki, T.; Tsuchiya, N.; Noguchi, M.; Yuzurihara, M.; Kase, Y.; Irahara, M. Associations of interleukin-6 with interleukin-1beta, interleukin-8 and macrophage inflammatory protein-1beta in midlife women. Cytokine, 2008, 41(3), 302-306.
[http://dx.doi.org/10.1016/j.cyto.2007.12.001] [PMID: 18226916]
[16]
Taleb-Belkadi, O.; Chaib, H.; Zemour, L.; Fatah, A.; Chafi, B.; Mekki, K. Lipid profile, inflammation, and oxidative status in peri- and postmenopausal women. Gynecol. Endocrinol., 2016, 32(12), 982-985.
[http://dx.doi.org/10.1080/09513590.2016.1214257] [PMID: 27558905]
[17]
Hong, S.C.; Yoo, S.W.; Cho, G.J.; Kim, T.; Hur, J.Y.; Park, Y.K.; Lee, K.W.; Kim, S.H. Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women. Menopause, 2007, 14(5), 835-840.
[http://dx.doi.org/10.1097/gme.0b013e31802cddca] [PMID: 17667144]
[18]
Perry, C.D.; Alekel, D.L.; Ritland, L.M.; Bhupathiraju, S.N.; Stewart, J.W.; Hanson, L.N.; Matvienko, O.A.; Kohut, M.L.; Reddy, M.B.; Van Loan, M.D.; Genschel, U. Centrally located body fat is related to inflammatory markers in healthy postmenopausal women. Menopause, 2008, 15(4 Pt 1), 619-627.
[http://dx.doi.org/10.1097/gme.0b013e318159f1a2] [PMID: 18202591]
[19]
Fan, H.; Chen, S.; Gao, B.; Ding, S.; Zhao, Q.; Li, C.; Asakawa, T. Risk analysis of systemic levels of estrogen and adipokines as well as estrogen receptors from PBMCs in childbearing and perimenopausal women with obesity. Diabetes Metab. Syndr. Obes., 2019, 12, 1287-1295.
[http://dx.doi.org/10.2147/DMSO.S206069] [PMID: 31534355]
[20]
Wong, E.; Freiberg, M.; Tracy, R.; Kuller, L. Epidemiology of cytokines: The women on the move through activity and nutrition (WOMAN) study. Am. J. Epidemiol., 2008, 168(4), 443-453.
[http://dx.doi.org/10.1093/aje/kwn132] [PMID: 18579536]
[21]
Gregorio-Arenas, E.; Ruiz-Cabello, P.; Camiletti-Moirón, D.; Moratalla-Cecilia, N.; Aranda, P.; López-Jurado, M.; Llopis, J.; Aparicio, V.A. The associations between physical fitness and cardiometabolic risk and body-size phenotypes in perimenopausal women. Maturitas, 2016, 92, 162-167.
[http://dx.doi.org/10.1016/j.maturitas.2016.08.008] [PMID: 27621255]
[22]
Collins, P.; Rosano, G.; Casey, C.; Daly, C.; Gambacciani, M.; Hadji, P.; Kaaja, R.; Mikkola, T.; Palacios, S.; Preston, R.; Simon, T.; Stevenson, J.; Stramba-Badiale, M. Management of cardiovascular risk in the perimenopausal women: a consensus statement of European cardiologists and gynecologists. Climacteric, 2007, 10(6), 508-526.
[http://dx.doi.org/10.1080/13697130701755213] [PMID: 18049944]
[23]
Harlow, S.D.; Gass, M.; Hall, J.E.; Lobo, R.; Maki, P.; Rebar, R.W.; Sherman, S.; Sluss, P.M.; de Villiers, T.J. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Fertil. Steril., 2012, 97(4), 843-851.
[http://dx.doi.org/10.1016/j.fertnstert.2012.01.128] [PMID: 22341880]
[24]
Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity. Geneva, June 3-5, 1997. Geneva:WHO, 1998.
[25]
Ho, S.Y.; Lam, T.H.; Janus, E.D. Waist to stature ratio is more strongly associated with cardiovascular risk factors than other simple anthropometric indices. Ann. Epidemiol., 2003, 13(10), 683-691.
[http://dx.doi.org/10.1016/S1047-2797(03)00067-X] [PMID: 14599732]
[26]
Anthropometry Procedures Manual Available at:, https://www.cdc.gov/nchs/data/nhanes/nhanes_07_08/manual_an.pdf(Accessed on April 20, 2018)..
[27]
Nascimento, J.X.; Chein, M.B.; de Sousa, R.M.; Ferreira, Ados.S.; Navarro, P.A.; Brito, L.M. Importance of lipid accumulation product index as a marker of CVD risk in PCOS women. Lipids Health Dis., 2015, 14, 62.
[http://dx.doi.org/10.1186/s12944-015-0061-y] [PMID: 26104466]
[28]
Galvão-Moreira, L.V.; Nascimento, A.C.B.; D’Albuquerque, I.M.S.C.; Sousa, M.A.S.; Brito, H.O.; Nascimento, M.D.D.S.B.; da Costa Chein, M.B.; Brito, L.M.O. Hormonal, metabolic and inflammatory circulating biomarker profiles in obese and non-obese Brazilian middle-aged women. PLoS One, 2019, 14(9),e0222239.
[http://dx.doi.org/10.1371/journal.pone.0222239] [PMID: 31509577]
[29]
Zivkovic, T.B.; Vuksanovic, M.; Jelic, M.A.; Stojanovic, J.; Buric, B.; Jojic, B.; Milic, N.; Vujovic, S. Obesity and metabolic syndrome during the menopause transition in Serbian women. Climacteric, 2011, 14(6), 643-648.
[http://dx.doi.org/10.3109/13697137.2011.569595] [PMID: 21878054]
[30]
Meyers, J.A.; Liu, A.Y.; McTiernan, A.; Wener, M.H.; Wood, B.; Weigle, D.S.; Sorensen, B.; Chen-Levy, Z.; Yasui, Y.; Boynton, A.; Potter, J.D.; Ulrich, C.M. Serum leptin concentrations and markers of immune function in overweight or obese postmenopausal women. J. Endocrinol., 2008, 199(1), 51-60.
[http://dx.doi.org/10.1677/JOE-07-0569] [PMID: 18614715]
[31]
Chedraui, P.; Jaramillo, W.; Pérez-López, F.R.; Escobar, G.S.; Morocho, N.; Hidalgo, L. Pro-inflammatory cytokine levels in postmenopausal women with the metabolic syndrome. Gynecol. Endocrinol., 2011, 27(9), 685-691.
[http://dx.doi.org/10.3109/09513590.2010.521270] [PMID: 20937002]
[32]
McMaster, W.G.; Kirabo, A.; Madhur, M.S.; Harrison, D.G. Inflammation, immunity, and hypertensive end-organ damage. Circ. Res., 2015, 116(6), 1022-1033.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.303697] [PMID: 25767287]
[33]
Chedraui, P.; Escobar, G.S.; Ramírez, C.; Pérez-López, F.R.; Hidalgo, L.; Mannella, P.; Genazzani, A.; Simoncini, T. Nitric oxide and pro-inflammatory cytokine serum levels in postmenopausal women with the metabolic syndrome. Gynecol. Endocrinol., 2012, 28(10), 787-791.
[http://dx.doi.org/10.3109/09513590.2012.671395] [PMID: 22468900]
[34]
Imayama, I.; Ulrich, C.M.; Alfano, C.M.; Wang, C.; Xiao, L.; Wener, M.H.; Campbell, K.L.; Duggan, C.; Foster-Schubert, K.E.; Kong, A.; Mason, C.E.; Wang, C.Y.; Blackburn, G.L.; Bain, C.E.; Thompson, H.J.; McTiernan, A. Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: A randomized controlled trial. Cancer Res., 2012, 72(9), 2314-2326.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3092] [PMID: 22549948]
[35]
Søreide, K. Receiver-operating characteristic curve analysis in diagnostic, prognostic and predictive biomarker research. J. Clin. Pathol., 2009, 62(1), 1-5.
[http://dx.doi.org/10.1136/jcp.2008.061010] [PMID: 18818262]
[36]
Camilleri, G.; Borg, M.; Brincat, S.; Schembri-Wismayer, P.; Brincat, M.; Calleja-Agius, J. The role of cytokines in cardiovascular disease in menopause. Climacteric, 2012, 15(6), 524-530.
[http://dx.doi.org/10.3109/13697137.2012.700743] [PMID: 22992012]
[37]
Ahtiainen, M.; Alen, M.; Pöllänen, E.; Pulkkinen, S.; Ronkainen, P.H.; Kujala, U.M.; Kaprio, J.; Sipilä, S.; Kovanen, V. Hormone therapy is associated with better body composition and adipokine/glucose profiles: a study with monozygotic co-twin control design. Menopause, 2012, 19(12), 1329-1335.
[http://dx.doi.org/10.1097/gme.0b013e31825a3344] [PMID: 22914204]
[38]
Deguchi, K.; Kamada, M.; Irahara, M.; Maegawa, M.; Yamamoto, S.; Ohmoto, Y.; Murata, K.; Yasui, T.; Yamano, S.; Aono, T. Postmenopausal changes in production of type 1 and type 2 cytokines and the effects of hormone replacement therapy. Menopause, 2001, 8(4), 266-273.
[http://dx.doi.org/10.1097/00042192-200107000-00008] [PMID: 11449084]
[39]
Aroor, A.R.; McKarns, S.; Demarco, V.G.; Jia, G.; Sowers, J.R. Maladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance. Metabolism, 2013, 62(11), 1543-1552.
[http://dx.doi.org/10.1016/j.metabol.2013.07.001] [PMID: 23932846]
[40]
Maiorino, M.I.; Schisano, B.; Di Palo, C.; Vietri, M.T.; Cioffi, M.; Giugliano, G.; Giugliano, D.; Esposito, K. Interleukin-20 circulating levels in obese women: effect of weight loss. Nutr. Metab. Cardiovasc. Dis., 2010, 20(3), 180-185.
[http://dx.doi.org/10.1016/j.numecd.2009.03.006] [PMID: 19481430]
[41]
Tajik, N.; Keshavarz, S.A.; Masoudkabir, F.; Djalali, M.; Sadrzadeh-Yeganeh, H.H.; Eshraghian, M.R.; Chamary, M.; Ahmadivand, Z.; Yazdani, T.; Javanbakht, M.H. Effect of diet-induced weight loss on inflammatory cytokines in obese women. J. Endocrinol. Invest., 2013, 36(4), 211-215.
[PMID: 22733212]
[42]
Esposito, K.; Pontillo, A.; Giugliano, F.; Giugliano, G.; Marfella, R.; Nicoletti, G.; Giugliano, D. Association of low interleukin-10 levels with the metabolic syndrome in obese women. J. Clin. Endocrinol. Metab., 2003, 88(3), 1055-1058.
[http://dx.doi.org/10.1210/jc.2002-021437] [PMID: 12629085]
[43]
Phillips, M.D.; Patrizi, R.M.; Cheek, D.J.; Wooten, J.S.; Barbee, J.J.; Mitchell, J.B. Resistance training reduces subclinical inflammation in obese, postmenopausal women. Med. Sci. Sports Exerc., 2012, 44(11), 2099-2110.
[http://dx.doi.org/10.1249/MSS.0b013e3182644984] [PMID: 22874536]
[44]
Molnár, I.; Bohaty, I.; Somogyiné-Vári, É. High prevalence of increased interleukin-17A serum levels in postmenopausal estrogen deficiency. Menopause, 2014, 21(7), 749-752.
[http://dx.doi.org/10.1097/GME.0000000000000125] [PMID: 24253487]
[45]
Zúñiga, L.A.; Shen, W.J.; Joyce-Shaikh, B.; Pyatnova, E.A.; Richards, A.G.; Thom, C.; Andrade, S.M.; Cua, D.J.; Kraemer, F.B.; Butcher, E.C. IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J. Immunol., 2010, 185(11), 6947-6959.
[http://dx.doi.org/10.4049/jimmunol.1001269] [PMID: 21037091]
[46]
Hong, C.P.; Park, A.; Yang, B.G.; Yun, C.H.; Kwak, M.J.; Lee, G.W.; Kim, J.H.; Jang, M.S.; Lee, E.J.; Jeun, E.J.; You, G.; Kim, K.S.; Choi, Y.; Park, J.H.; Hwang, D.; Im, S.H.; Kim, J.F.; Kim, Y.K.; Seoh, J.Y.; Surh, C.D.; Kim, Y.M.; Jang, M.H. Gut-specific delivery of T-helper 17 cells reduces obesity and insulin resistance in mice. Gastroenterology, 2017, 152(8), 1998-2010.
[http://dx.doi.org/10.1053/j.gastro.2017.02.016] [PMID: 28246016]
[47]
Winer, S.; Paltser, G.; Chan, Y.; Tsui, H.; Engleman, E.; Winer, D.; Dosch, H.M. Obesity predisposes to Th17 bias. Eur. J. Immunol., 2009, 39(9), 2629-2635.
[http://dx.doi.org/10.1002/eji.200838893] [PMID: 19662632]
[48]
Chedraui, P.; Escobar, G.S.; Pérez-López, F.R.; Palla, G.; Montt-Guevara, M.; Cecchi, E.; Genazzani, A.R.; Simoncini, T. Angiogenesis, inflammation and endothelial function in postmenopausal women screened for the metabolic syndrome. Maturitas, 2014, 77(4), 370-374.
[http://dx.doi.org/10.1016/j.maturitas.2014.01.014] [PMID: 24598235]
[49]
Riesco, E.; Tessier, S.; Lacaille, M.; Pérusse, F.; Côté, M.; Després, J.P.; Bergeron, J.; Weisnagel, J.S.; Doré, J.; Mauriège, P. Impact of a moderate-intensity walking program on cardiometabolic risk markers in overweight to obese women: is there any influence of menopause? Menopause, 2013, 20(2), 185-193.
[http://dx.doi.org/10.1097/GME.0b013e31826f7ebf] [PMID: 23096247]


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VOLUME: 20
ISSUE: 6
Year: 2020
Published on: 17 July, 2020
Page: [917 - 923]
Pages: 7
DOI: 10.2174/1871530320666191220110503
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