Interleukin 1-beta is Linked to Chronic Low-Grade Inflammation and Cardiovascular Risk Factors in Overweight Adolescents

Author(s): Gisele A. Amaral, Josilene D. Alves, Adenilda C. Honorio-França, Danny L. Fagundes, Gabriel Gomes Araujo, Nubia S. Lobato, Victor V. Lima, Fernanda R. Giachini*

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:

Aim: We hypothesized that IL-1β concentrations are augmented in overweight adolescents, who do not display metabolic syndrome. Additionally, we aimed to correlate the IL-1β concentrations with several established risk factors for CVD.

Methods: Overweight or control subjects, aging from 14-18 years, were classified according to their adjusted body mass index and evaluated for biochemical and anthropometric parameters. The proinflammatory cytokine IL-1β was assessed in the serum.

Results: Increased body fat percentage, waist circumference, triglycerides, total cholesterol, Very Low-Density Lipoprotein (VLDL) cholesterol, Low-Density Lipoprotein (LDL) cholesterol, Castelli I index, IL-1β, and IL-8 levels, were observed in overweight adolescents. No differences were observed in systolic blood pressure, diastolic blood pressure, glucose or High-Density Lipoprotein (HDL) cholesterol. Positive correlations between IL-1β with anthropometric and or biochemical parameters were found.

Conclusion: In conclusion, increased IL-1β levels correlate to dyslipidemic factors and may further support low-grade inflammation. IL-1β may further predict the early onset of cardiovascular disease in this population, taking into consideration its important regulatory role.

Keywords: Childhood, obesity, cytokine, inflammation, dyslipidemia, interleukins.

[1]
Kelishadi, R.; Roufarshbaf, M.; Soheili, S.; Payghambarzadeh, F.; Masjedi, M. Association of Childhood Obesity and the Immune System: A Systematic Review of Reviews. Child. Obes., 2017, 13(4), 332-346.
[http://dx.doi.org/10.1089/chi.2016.0176] [PMID: 28604080]
[2]
Ayer, J.; Charakida, M.; Deanfield, J.E.; Celermajer, D.S. Lifetime risk: Childhood obesity and cardiovascular risk. Eur. Soc. Cardiol, 2015, 1-8.
[http://dx.doi.org/10.1093/eurheartj/ehv089]
[3]
Smith, K.J.; Magnussen, C.G.; Pahkala, K.; Koskinen, J.; Sabin, M.A.; Hutri-Kähönen, N.; Kähönen, M.; Laitinen, T.; Tammelin, T.; Tossavainen, P.; Jokinen, E.; Viikari, J.S.A.; Juonala, M.; Raitakari, O.T. Youth to adult body mass index trajectories as a predictor of metabolically healthy obesity in adulthood. Eur. J. Public Health, 2020, 30(1), 195-199.
[http://dx.doi.org/10.1093/eurpub/ckz109] [PMID: 31169878]
[4]
Kaplan, A.; Hardjojo, A.; Yu, S.; Price, D. Asthma across age: Insights from primary care. Front Pediatr., 2019, 7, 162.
[http://dx.doi.org/10.3389/fped.2019.00162] [PMID: 31131265]
[5]
Herle, M.; Fildes, A.; Steinsbekk, S.; Rijsdijk, F.; Llewellyn, C.H. Emotional over- and under-eating in early childhood are learned not inherited. Sci. Rep., 2017, 7(1), 9092.
[http://dx.doi.org/10.1038/s41598-017-09519-0] [PMID: 28831105]
[6]
Amano, S.U.; Cohen, J.L.; Vangala, P.; Tencerova, M.; Nicoloro, S.M.; Yawe, J.C.; Shen, Y.; Czech, M.P.; Aouadi, M. Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab., 2014, 19(1), 162-171.
[http://dx.doi.org/10.1016/j.cmet.2013.11.017] [PMID: 24374218]
[7]
Kaválková, P.; Mráz, M.; Trachta, P.; Kloučková, J.; Cinkajzlová, A.; Lacinová, Z.; Haluzíková, D.; Beneš, M.; Vlasáková, Z.; Burda, V.; Novák, D.; Petr, T.; Vítek, L.; Pelikánová, T.; Haluzík, M. Endocrine effects of duodenal-jejunal exclusion in obese patients with type 2 diabetes mellitus. J. Endocrinol., 2016, 231(1), 11-22.
[http://dx.doi.org/10.1530/JOE-16-0206] [PMID: 27474690]
[8]
Bays, H.E. Adiposopathy is “sick fat” a cardiovascular disease? J. Am. Coll. Cardiol., 2011, 57(25), 2461-2473.
[http://dx.doi.org/10.1016/j.jacc.2011.02.038] [PMID: 21679848]
[9]
Blüher, M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract. Res. Clin. Endocrinol. Metab., 2013, 27(2), 163-177.
[http://dx.doi.org/10.1016/j.beem.2013.02.005] [PMID: 23731879]
[10]
Klöting, N.; Blüher, M. Adipocyte dysfunction, inflammation and metabolic syndrome. Rev. Endocr. Metab. Disord., 2014, 15(4), 277-287.
[http://dx.doi.org/10.1007/s11154-014-9301-0] [PMID: 25344447]
[11]
Mattos, R.T.; Medeiros, N.I.; Menezes, C.A.; Fares, R.C.G.; Franco, E.P.; Dutra, W.O.; Rios-Santos, F.; Correa-Oliveira, R.; Gomes, J.A.S. Chronic low-grade inflammation in childhood obesity is associated with decreased IL-10 expression by monocyte subsets. PLoS One, 2016, 11(12)e0168610
[http://dx.doi.org/10.1371/journal.pone.0168610] [PMID: 27977792]
[12]
Antunes, B.de M.; Monteiro, P.A.; Silveira, L.S.; Brunholi, Cde.C.; Lira, F.S.; Freitas Júnior, I.F. Macronutrient intake is correlated with dyslipidemia and low-grade inflammation in childhood obesity but mostly in male obese. Nutr. Hosp., 2015, 32(3), 997-1003.
[http://dx.doi.org/10.3305/nh.2015.32.3.9289] [PMID: 26319811]
[13]
Nicol, L.E.; Grant, W.F.; Comstock, S.M.; Nguyen, M.L.; Smith, M.S.; Grove, K.L.; Marks, D.L. Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates. J. Endocrinol., 2013, 217(2), 207-213.
[http://dx.doi.org/10.1530/JOE-12-0424] [PMID: 23420316]
[14]
Engin, A.B. Adipocyte-Macrophage Cross-Talk in Obesity. In: Advances in Experimental Medicine and Biology; Springer New York LLC, 2017; 960, pp. 327-343.
[http://dx.doi.org/ 10.1007/978-3-319-48382-5_14]
[15]
Niu, J.; Gilliland, M.G.; Jin, Z.; Kolattukudy, P.E.; Hoffman, W.H. MCP-1and IL-1β expression in the myocardia of two young patients with Type 1 diabetes mellitus and fatal diabetic ketoacidosis. Exp. Mol. Pathol., 2014, 96(1), 71-79.
[http://dx.doi.org/10.1016/j.yexmp.2013.11.001] [PMID: 24246157]
[16]
Nascimento, H.; Vieira, E.; Coimbra, S.; Catarino, C.; Costa, E.; Bronze-da-Rocha, E.; Rocha-Pereira, P.; Carvalho, M.; Ferreira Mansilha, H.; Rêgo, C.; Dos Santos, R.; Santos-Silva, A.; Belo, L. Adipokine gene single-nucleotide polymorphisms in portuguese obese adolescents: associations with plasma concentrations of adiponectin, resistin, IL-6, IL-1β, and TNF-α. Child. Obes., 2016, 12(4), 300-313.
[http://dx.doi.org/10.1089/chi.2015.0235] [PMID: 27159547]
[17]
Niu, J.; Gilliland, M.G.F.; Jin, Z.; Kolattukudy, P.E.; Hoffman, W.H. MCP-1and IL-1β expression in the myocardia of two young patients with Type 1 diabetes mellitus and fatal diabetic ketoacidosis. Exp. Mol. Pathol., 2014, 96(1), 71-79.
[http://dx.doi.org/10.1016/j.yexmp.2013.11.001] [PMID: 24246157]
[18]
Nicol, L.E.; Grant, W.F.; Comstock, S.M.; Nguyen, M.L.; Smith, M.S.; Grove, K.L.; Marks, D.L. Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates. J. Endocrinol., 2013, 217(2), 207-213.
[http://dx.doi.org/10.1530/JOE-12-0424] [PMID: 23420316]
[19]
Cole, T.J.; Bellizzi, M.C.; Flegal, K.M.; Dietz, W.H. Establishing a standard definition for child overweight and obesity worldwide: International survey. BMJ, 2000, 320(7244), 1240-1243.
[http://dx.doi.org/10.1136/bmj.320.7244.1240] [PMID: 10797032]
[20]
Fornage, M.; Gillespie, C.; Isasi, C.R.; Lichtman, J.H.; Lisabeth, L. Heart disease and stroke statistics - 2017 Update. Circulation, 2017, 135(10), e146-e603.
[http://dx.doi.org/10.1161/CIR.0000000000000485.Heart]
[21]
Teng, K.T.; Chang, C.Y.; Chang, L.F.; Nesaretnam, K. Modulation of obesity-induced inflammation by dietary fats: mechanisms and clinical evidence. Nutr. J., 2014, 13(1), 12.
[http://dx.doi.org/10.1186/1475-2891-13-12] [PMID: 24476102]
[22]
Looker, H.C.; Colombo, M.; Agakov, F.; Zeller, T.; Groop, L.; Thorand, B.; Palmer, C.N.; Hamsten, A.; De Faire, U.; Nogoceke, E. Protein biomarkers for the prediction of cardiovascular disease in Type 2 Diabetes. Diabetologia, 2015, 58, 1363-1371.
[23]
Herder, C.; Dalmas, E.; Böni-Schnetzler, M.; Donath, M.Y. The IL-1 Pathway in Type 2 diabetes and cardiovascular complications. Trends Endocrinol. Metab., 2015, 26(10), 551-563.
[24]
Ridker, P.M.; Thuren, T.; Zalewski, A.; Libby, P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: Rationale and design of the canakinumab anti-inflammatory thrombosis outcomes study (CANTOS). Am. Heart J., 2011, 162(4), 597-605.
[http://dx.doi.org/10.1016/j.ahj.2011.06.012] [PMID: 21982649]
[25]
Yang, Y.; Zhong, Z.; Wang, B.; Xia, X.; Yao, W.; Huang, L.; Wang, Y.; Ding, W. Early-life high-fat diet-induced obesity programs hippocampal development and cognitive functions via regulation of gut commensal Akkermansia muciniphila. Neuropsychopharmacology, 2019, 44(12), 2054-2064.
[http://dx.doi.org/10.1038/s41386-019-0437-1] [PMID: 31207607]
[26]
Shoda, H.; Nagafuchi, Y.; Tsuchida, Y.; Sakurai, K.; Sumitomo, S.; Fujio, K.; Yamamoto, K. Increased serum concentrations of IL-1 beta, IL-21 and Th17 cells in overweight patients with rheumatoid arthritis. Arthritis Res. Ther., 2017, 19(1), 111.
[http://dx.doi.org/10.1186/s13075-017-1308-y] [PMID: 28569167]
[27]
Coimbra, S.; Nascimento, H.; Bronze-da-rocha, E.; Catarino, C. Adipokine gene single-nucleotide polymorphisms in Portuguese obese adolescents: Associations with plasma concentrations of adiponectin, resistin, IL-6, IL-1b, and TNF-A. Child. Obes., 2016, 12(4), 300-313.
[http://dx.doi.org/10.1089/chi.2015.0235]
[28]
Ghomari-Boukhatem, H.; Bouchouicha, A.; Mekki, K.; Chenni, K.; Belhadj, M.; Bouchenak, M. Blood pressure, dyslipidemia and inflammatory factors are related to body mass index in scholar adolescents. Arch. Med. Sci., 2017, 13(1), 46-52.
[http://dx.doi.org/10.5114/aoms.2017.64713] [PMID: 28144254]
[29]
Romuk, E.; Skrzep-Poloczek, B.; Wojciechowska, C.; Tomasik, A.; Birkner, E.; Wodniecki, J.; Gabrylewicz, B.; Ochala, A.; Tendera, M. Selectin-P and interleukin-8 plasma levels in coronary heart disease patients. Eur. J. Clin. Invest., 2002, 32(9), 657-661.
[http://dx.doi.org/10.1046/j.1365-2362.2002.01053.x] [PMID: 12486864]
[30]
Boekholdt, S.M.; Peters, R.J.G.; Hack, C.E.; Day, N.E.; Luben, R.; Bingham, S.A.; Wareham, N.J.; Reitsma, P.H.; Khaw, K.T. IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: The EPIC-Norfolk prospective population study. Arterioscler. Thromb. Vasc. Biol., 2004, 24(8), 1503-1508.
[http://dx.doi.org/10.1161/01.ATV.0000134294.54422.2e] [PMID: 15178568]
[31]
Levine, M.E.; Cole, S.W.; Weir, D.R.; Crimmins, E.M. Childhood and later life stressors and increased inflammatory gene expression at older ages. Soc. Sci. Med., 2015, 130, 16-22.
[http://dx.doi.org/10.1016/j.socscimed.2015.01.030] [PMID: 25658624]
[32]
Nehete, P.; Magden, E.R.; Nehete, B.; Hanley, P.W.; Abee, C.R. Obesity related alterations in plasma cytokines and metabolic hormones in chimpanzees. Int. J. Inflamation, 2014, 2014 856749
[33]
Sobesky, J.L.; Barrientos, R.M.; De May, H.S.; Thompson, B.M.; Weber, M.D.; Watkins, L.R.; Maier, S.F. High-fat diet consumption disrupts memory and primes elevations in hippocampal IL-1β, an effect that can be prevented with dietary reversal or IL-1 receptor antagonism. Brain Behav. Immun., 2014, 42, 22-32.
[http://dx.doi.org/10.1016/j.bbi.2014.06.017] [PMID: 24998196]
[34]
Jung, C.; Gerdes, N.; Fritzenwanger, M.; Figulla, H.R. Circulating levels of interleukin-1 family cytokines in overweight adolescents. Mediators Inflamm., 2010, 2010, 1-7.
[http://dx.doi.org/10.1155/2010/958403]
[35]
Puertas, A.M.; Maroto, J.A.; Fernández-Barbero, A.; De Las Nieves, F.J. Postprandial macrophage-derived il-1b stimulates insulin, and both synergistically promote glucose disposal and inflammation. Colloids Surf. A Physicochem. Eng. Asp., 2017, 151(3), 473-481.
[http://dx.doi.org/10.1016/S0927-7757(98)00840-1]
[36]
Alomar, S.Y.; Zaibi, M.S.; Kępczyńska, M.A.; Gentili, A.; Alkhuriji, A.; Mansour, L.; Dar, J.A.; Trayhurn, P.; Alkhuriji, A.; Mansour, L. PCR array and protein array studies demonstrate that IL-1β (interleukin-1β) stimulates the expression and secretion of multiple cytokines and chemokines in human adipocytes. Arch. Physiol. Biochem., 2015, 121(5), 187-193.
[http://dx.doi.org/10.3109/13813455.2015.1087034] [PMID: 26471721]
[37]
McGillicuddy, F.C.; Harford, K.A.; Reynolds, C.M.; Oliver, E.; Claessens, M.; Mills, K.H.G.; Roche, H.M. Lack of interleukin-1 receptor I (IL-1RI) protects mice from high-fat diet-induced adipose tissue inflammation coincident with improved glucose homeostasis. Diabetes, 2011, 60(6), 1688-1698.
[http://dx.doi.org/10.2337/db10-1278] [PMID: 21515850]
[38]
Alomar, S.Y.; Gentili, A.; Zaibi, M.S.; Kępczyńska, M.A.; Trayhurn, P. IL-1β (Interleukin-1β) stimulates the production and release of multiple cytokines and chemokinesby human. Arch. Physiol. Biochem., 2016, 122(3), 117-122.
[http://dx.doi.org/10.3109/13813455.2016.1156706] [PMID: 26890442]
[39]
Morandi, A.; Maffeis, C. Predictors of metabolic risk in childhood obesity. Horm. Res. Paediatr., 2014, 82(1), 3-11.
[http://dx.doi.org/10.1159/000362237] [PMID: 24923289]
[40]
Morrison, J.A.; Friedman, L.A.; Harlan, W.R.; Harlan, L.C.; Barton, B.A.; Schreiber, G.B.; Klein, D.J.; Background, A. Development of the metabolic syndrome in black and white adolescent girls: a longitudinal assessment. Pediatrics, 2005, 116(5), 1178-1182.
[http://dx.doi.org/10.1542/peds.2004-2358] [PMID: 16264006]
[41]
Nicklin, M.J.; Hughes, D.E.; Barton, J.L.; Ure, J.M.; Duff, G.W. Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene. J. Exp. Med., 2000, 191(2), 303-312.
[http://dx.doi.org/10.1084/jem.191.2.303] [PMID: 10637274]
[42]
Chamberlain, J.; Francis, S.; Brookes, Z.; Shaw, G.; Graham, D.; Alp, N.J.; Dower, S.; Crossman, D.C. Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding. PLoS One, 2009, 4(4)e5073
[http://dx.doi.org/10.1371/journal.pone.0005073] [PMID: 19347044]
[43]
Vicenová, B.; Vopálenský, V.; Burýsek, L.; Pospísek, M. Emerging role of interleukin-1 in cardiovascular diseases. Physiol. Res., 2009, 58(4), 481-498.
[PMID: 19093736]
[44]
Carstensen, M.; Herder, C.; Kivimäki, M.; Jokela, M.; Roden, M.; Shipley, M.J.; Witte, D.R.; Brunner, E.J.; Tabák, A.G.; Accelerated Increase, A.G. Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes, 2010, 59(5), 1222-1227.
[http://dx.doi.org/10.2337/db09-1199] [PMID: 20185814]
[45]
Gao, D.; Madi, M.; Ding, C.; Fok, M.; Steele, T.; Ford, C.; Hunter, L.; Bing, C. Interleukin-1β mediates macrophage-induced impairment of insulin signaling in human primary adipocytes. Am. J. Physiol. Endocrinol. Metab., 2014, 307(3), E289-E304.
[http://dx.doi.org/10.1152/ajpendo.00430.2013] [PMID: 24918199]
[46]
Bibbins-Domingo, K.; Coxson, P.; Pletcher, M.J.; Lightwood, J.; Goldman, L. Adolescent overweight and future adult coronary heart disease. N. Engl. J. Med., 2007, 357(23), 2371-2379.
[http://dx.doi.org/10.1056/NEJMsa073166] [PMID: 18057339]


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VOLUME: 20
ISSUE: 6
Year: 2020
Published on: 17 July, 2020
Page: [887 - 894]
Pages: 8
DOI: 10.2174/1871530319666191116141159
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