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Published in: BMC Pediatrics 1/2013

Open Access 01-12-2013 | Research article

Chemokine (C-C motif) Ligand 2 is a potential biomarker of inflammation & physical fitness in obese children: a cross-sectional study

Authors: M Constantine Samaan, Joyce Obeid, Thanh Nguyen, Lehana Thabane, Brian W Timmons

Published in: BMC Pediatrics | Issue 1/2013

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Abstract

Background

Obesity is a global epidemic that is impacting children around the world. Obesity is a chronic inflammatory state with enhanced production of multiple cytokines and chemokines. Chemokine (C-C motif) Ligand 2 (CCL2) is produced by immune and metabolic cells and attracts immune cells into liver, muscle and adipose tissue, resulting in initiation and propagation of the inflammatory response in obesity. How obesity and fitness affect the production of this chemokine in children is unknown.
This study tested the hypotheses that CCL2 levels are higher in obese children when compared to lean controls, and that fitness modulates CCL2 levels allowing its use as a biomarker of fitness.

Methods

This was a cross sectional case–control study conducted in a Pediatric Tertiary care center in Hamilton, Ontario, Canada. Controls were recruited from the community. This study recruited overweight/obese children (BMI ≥ 85th percentile, n = 18, 9 female, mean age 14.0 ± 2.6 years) and lean controls (BMI < 85th percentile, n = 18, 8 female, mean age 14.0 ± 2.6 years) matched for age, sex and biological maturation.
Aerobic fitness test was done using a cycle ergometer performing the McMaster All-Out Progressive Continuous Cycling test to exhaustion to determine peak oxygen uptake. Fasting CCL2 samples were taken prior to test. Categorical variables including subject categorization into different aerobic fitness levels in overweight/obese and lean children was reported based on the median split in each group.

Results

Obese participants had significantly higher CCL2 levels when compared to lean group (150.4 ± 61.85 pg/ml versus 112.7 ± 38 pg/ml, p-value 0.034).
To establish if CCL2 is a biomarker of fitness, we divided the groups based on their fitness levels. There was a main effect for group (F (3,32) = 3.2, p = 0.036). Obese high fitness group were similar to lean unfit and fit participants. Post-hoc analysis revealed that the overweight/obese low fitness group had significantly higher level of CCL2 compared to the lean low fitness group when adjusted to age, sex and maturity offset (F (3,29) = 3.1, p = 0.04).

Conclusions

CCL2 serves a dual role as a potential biomarker of inflammation and fitness in obese children.
Appendix
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Literature
1.
go back to reference Reilly JJ: Obesity in childhood and adolescence: evidence based clinical and public health perspectives. Postgrad Med J. 2006, 82 (969): 429-437. 10.1136/pgmj.2005.043836.CrossRefPubMedPubMedCentral Reilly JJ: Obesity in childhood and adolescence: evidence based clinical and public health perspectives. Postgrad Med J. 2006, 82 (969): 429-437. 10.1136/pgmj.2005.043836.CrossRefPubMedPubMedCentral
2.
go back to reference de Onis M, Blössner M, Borghi E: Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr. 2010, 92 (5): 1257-1264. 10.3945/ajcn.2010.29786.CrossRefPubMed de Onis M, Blössner M, Borghi E: Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr. 2010, 92 (5): 1257-1264. 10.3945/ajcn.2010.29786.CrossRefPubMed
4.
go back to reference Wang Y, Lobstein TIM: Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes. 2006, 1 (1): 11-25. 10.1080/17477160600586747.CrossRefPubMed Wang Y, Lobstein TIM: Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes. 2006, 1 (1): 11-25. 10.1080/17477160600586747.CrossRefPubMed
5.
go back to reference Ludwig DS, Peterson KE, Gortmaker SL: Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet. 2001, 357 (9255): 505-508. 10.1016/S0140-6736(00)04041-1.CrossRefPubMed Ludwig DS, Peterson KE, Gortmaker SL: Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet. 2001, 357 (9255): 505-508. 10.1016/S0140-6736(00)04041-1.CrossRefPubMed
6.
go back to reference Ebbeling CB, Pawlak DB, Ludwig DS: Childhood obesity: public-health crisis, common sense cure. Lancet. 2002, 360 (9331): 473-482. 10.1016/S0140-6736(02)09678-2.CrossRefPubMed Ebbeling CB, Pawlak DB, Ludwig DS: Childhood obesity: public-health crisis, common sense cure. Lancet. 2002, 360 (9331): 473-482. 10.1016/S0140-6736(02)09678-2.CrossRefPubMed
7.
go back to reference Yannakoulia M, Ntalla I, Papoutsakis C, Farmaki AE, Dedoussis GV: Consumption of vegetables, cooked meals, and eating dinner is negatively associated with overweight status in children. J Pediatr. 2010, 157 (5): 815-820. 10.1016/j.jpeds.2010.04.077.CrossRefPubMed Yannakoulia M, Ntalla I, Papoutsakis C, Farmaki AE, Dedoussis GV: Consumption of vegetables, cooked meals, and eating dinner is negatively associated with overweight status in children. J Pediatr. 2010, 157 (5): 815-820. 10.1016/j.jpeds.2010.04.077.CrossRefPubMed
8.
go back to reference Martinez-Gomez D, Eisenmann JC, Gomez-Martinez S, Hill EE, Zapatera B, Veiga OL, Marcos A: Sleep duration and emerging cardiometabolic risk markers in adolescents. The AFINOS study. Sleep Med. 2011, 12 (10): 997-1002. 10.1016/j.sleep.2011.05.009.CrossRefPubMed Martinez-Gomez D, Eisenmann JC, Gomez-Martinez S, Hill EE, Zapatera B, Veiga OL, Marcos A: Sleep duration and emerging cardiometabolic risk markers in adolescents. The AFINOS study. Sleep Med. 2011, 12 (10): 997-1002. 10.1016/j.sleep.2011.05.009.CrossRefPubMed
9.
go back to reference Cappuccio FP, Taggart FM, Kandala NB, Currie A, Peile E, Stranges S, Miller MA: Meta-analysis of short sleep duration and obesity in children and adults. Sleep. 2008, 31 (5): 619-626.PubMedPubMedCentral Cappuccio FP, Taggart FM, Kandala NB, Currie A, Peile E, Stranges S, Miller MA: Meta-analysis of short sleep duration and obesity in children and adults. Sleep. 2008, 31 (5): 619-626.PubMedPubMedCentral
10.
go back to reference Freedman DS, Mei Z, Srinivasan SR, Berenson GS, Dietz WH: Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study. J Pediatr. 2007, 150 (1): 12-17. 10.1016/j.jpeds.2006.08.042. e12CrossRefPubMed Freedman DS, Mei Z, Srinivasan SR, Berenson GS, Dietz WH: Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study. J Pediatr. 2007, 150 (1): 12-17. 10.1016/j.jpeds.2006.08.042. e12CrossRefPubMed
11.
go back to reference Nader PR, O’Brien M, Houts R, Bradley R, Belsky J, Crosnoe R, Friedman S, Mei Z, Susman EJ: Identifying risk for obesity in early childhood. Pediatrics. 2006, 118 (3): e594-601. 10.1542/peds.2005-2801.CrossRefPubMed Nader PR, O’Brien M, Houts R, Bradley R, Belsky J, Crosnoe R, Friedman S, Mei Z, Susman EJ: Identifying risk for obesity in early childhood. Pediatrics. 2006, 118 (3): e594-601. 10.1542/peds.2005-2801.CrossRefPubMed
12.
go back to reference Daniels SR, Arnett DK, Eckel RH, Gidding SS, Hayman LL, Kumanyika S, Robinson TN, Scott BJ, St Jeor S, Williams CL: Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation. 2005, 111 (15): 1999-2012. 10.1161/01.CIR.0000161369.71722.10.CrossRefPubMed Daniels SR, Arnett DK, Eckel RH, Gidding SS, Hayman LL, Kumanyika S, Robinson TN, Scott BJ, St Jeor S, Williams CL: Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation. 2005, 111 (15): 1999-2012. 10.1161/01.CIR.0000161369.71722.10.CrossRefPubMed
14.
go back to reference Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW: Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003, 112 (12): 1796-1808.CrossRefPubMedPubMedCentral Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW: Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003, 112 (12): 1796-1808.CrossRefPubMedPubMedCentral
15.
go back to reference Varma V, Yao-Borengasser A, Rasouli N, Nolen GT, Phanavanh B, Starks T, Gurley C, Simpson P, McGehee RE, Kern PA: Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action. Am J Physiol Endocrinol Metab. 2009, 296 (6): E1300-1310. 10.1152/ajpendo.90885.2008.CrossRefPubMedPubMedCentral Varma V, Yao-Borengasser A, Rasouli N, Nolen GT, Phanavanh B, Starks T, Gurley C, Simpson P, McGehee RE, Kern PA: Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action. Am J Physiol Endocrinol Metab. 2009, 296 (6): E1300-1310. 10.1152/ajpendo.90885.2008.CrossRefPubMedPubMedCentral
16.
go back to reference Bonecchi R, Galliera E, Borroni EM, Corsi MM, Locati M, Mantovani A: Chemokines and chemokine receptors: an overview. Front Biosci. 2009, 14: 540-551.CrossRef Bonecchi R, Galliera E, Borroni EM, Corsi MM, Locati M, Mantovani A: Chemokines and chemokine receptors: an overview. Front Biosci. 2009, 14: 540-551.CrossRef
17.
go back to reference Sartipy P, Loskutoff DJ: Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA. 2003, 100 (12): 7265-7270. 10.1073/pnas.1133870100.CrossRefPubMedPubMedCentral Sartipy P, Loskutoff DJ: Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA. 2003, 100 (12): 7265-7270. 10.1073/pnas.1133870100.CrossRefPubMedPubMedCentral
18.
go back to reference Arner E, Mejhert N, Kulyté A, Balwierz PJ, Pachkov M, Cormont M, Lorente-Cebrián S, Ehrlund A, Laurencikiene J, Hedén P: Adipose tissue MicroRNAs as regulators of CCL2 production in human obesity. Diabetes. 2012, 61 (8): 1986-1993. 10.2337/db11-1508.CrossRefPubMedPubMedCentral Arner E, Mejhert N, Kulyté A, Balwierz PJ, Pachkov M, Cormont M, Lorente-Cebrián S, Ehrlund A, Laurencikiene J, Hedén P: Adipose tissue MicroRNAs as regulators of CCL2 production in human obesity. Diabetes. 2012, 61 (8): 1986-1993. 10.2337/db11-1508.CrossRefPubMedPubMedCentral
19.
go back to reference Yang S, IglayReger H, Kadouh H, Bodary P: Inhibition of the chemokine (C–C motif) ligand 2/chemokine (C–C motif) receptor 2 pathway attenuates hyperglycaemia and inflammation in a mouse model of hepatic steatosis and lipoatrophy. Diabetologia. 2009, 52 (5): 972-981. 10.1007/s00125-009-1309-8.CrossRefPubMed Yang S, IglayReger H, Kadouh H, Bodary P: Inhibition of the chemokine (C–C motif) ligand 2/chemokine (C–C motif) receptor 2 pathway attenuates hyperglycaemia and inflammation in a mouse model of hepatic steatosis and lipoatrophy. Diabetologia. 2009, 52 (5): 972-981. 10.1007/s00125-009-1309-8.CrossRefPubMed
20.
go back to reference Yu X, Dluz S, Graves DT, Zhang L, Antoniades HN, Hollander W, Prusty S, Valente AJ, Schwartz CJ, Sonenshein GE: Elevated expression of monocyte chemoattractant protein 1 by vascular smooth muscle cells in hypercholesterolemic primates. Proc Natl Acad Sci. 1992, 89 (15): 6953-6957. 10.1073/pnas.89.15.6953.CrossRefPubMedPubMedCentral Yu X, Dluz S, Graves DT, Zhang L, Antoniades HN, Hollander W, Prusty S, Valente AJ, Schwartz CJ, Sonenshein GE: Elevated expression of monocyte chemoattractant protein 1 by vascular smooth muscle cells in hypercholesterolemic primates. Proc Natl Acad Sci. 1992, 89 (15): 6953-6957. 10.1073/pnas.89.15.6953.CrossRefPubMedPubMedCentral
21.
go back to reference Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE, Kwon BS, Erickson KL, Yu R: Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes. 2006, 30 (9): 1347-1355. 10.1038/sj.ijo.0803259.CrossRef Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE, Kwon BS, Erickson KL, Yu R: Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes. 2006, 30 (9): 1347-1355. 10.1038/sj.ijo.0803259.CrossRef
22.
go back to reference Roth CL, Kratz M, Ralston MM, Reinehr T: Changes in adipose-derived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children. Metabolism. 2011, 60 (4): 445-452. 10.1016/j.metabol.2010.03.023.CrossRefPubMed Roth CL, Kratz M, Ralston MM, Reinehr T: Changes in adipose-derived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children. Metabolism. 2011, 60 (4): 445-452. 10.1016/j.metabol.2010.03.023.CrossRefPubMed
23.
go back to reference Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE, Kwon BS, Erickson KL, Yu R: Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond). 2006, 30 (9): 1347-1355. 10.1038/sj.ijo.0803259.CrossRef Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE, Kwon BS, Erickson KL, Yu R: Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond). 2006, 30 (9): 1347-1355. 10.1038/sj.ijo.0803259.CrossRef
24.
go back to reference Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, Ohtsuka-Kowatari N, Kumagai K, Sakamoto K, Kobayashi M: Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem. 2006, 281 (36): 26602-26614. 10.1074/jbc.M601284200.CrossRefPubMed Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, Ohtsuka-Kowatari N, Kumagai K, Sakamoto K, Kobayashi M: Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem. 2006, 281 (36): 26602-26614. 10.1074/jbc.M601284200.CrossRefPubMed
25.
go back to reference Deepa R, Velmurugan K, Arvind K, Sivaram P, Sientay C, Uday S, Mohan V: Serum levels of interleukin 6, C-reactive protein, vascular cell adhesion molecule 1, and monocyte chemotactic protein 1 in relation to insulin resistance and glucose intolerance–the Chennai Urban Rural Epidemiology Study (CURES). Metabolism. 2006, 55 (9): 1232-1238. 10.1016/j.metabol.2006.05.008.CrossRefPubMed Deepa R, Velmurugan K, Arvind K, Sivaram P, Sientay C, Uday S, Mohan V: Serum levels of interleukin 6, C-reactive protein, vascular cell adhesion molecule 1, and monocyte chemotactic protein 1 in relation to insulin resistance and glucose intolerance–the Chennai Urban Rural Epidemiology Study (CURES). Metabolism. 2006, 55 (9): 1232-1238. 10.1016/j.metabol.2006.05.008.CrossRefPubMed
26.
go back to reference Ezenwaka CE, Nwagbara E, Seales D, Okali F, Sell H, Eckel J: Insulin resistance, leptin and monocyte chemotactic protein-1 levels in diabetic and non-diabetic Afro-Caribbean subjects. Arch Physiol Biochem. 2009, 115 (1): 22-27. 10.1080/13813450802676343.CrossRefPubMed Ezenwaka CE, Nwagbara E, Seales D, Okali F, Sell H, Eckel J: Insulin resistance, leptin and monocyte chemotactic protein-1 levels in diabetic and non-diabetic Afro-Caribbean subjects. Arch Physiol Biochem. 2009, 115 (1): 22-27. 10.1080/13813450802676343.CrossRefPubMed
27.
go back to reference Combadiere C, Potteaux S, Rodero M, Simon T, Pezard A, Esposito B, Merval R, Proudfoot A, Tedgui A, Mallat Z: Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation. 2008, 117 (13): 1649-1657. 10.1161/CIRCULATIONAHA.107.745091.CrossRefPubMed Combadiere C, Potteaux S, Rodero M, Simon T, Pezard A, Esposito B, Merval R, Proudfoot A, Tedgui A, Mallat Z: Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation. 2008, 117 (13): 1649-1657. 10.1161/CIRCULATIONAHA.107.745091.CrossRefPubMed
28.
go back to reference Chen Y-W, Hubal MJ, Hoffman EP, Thompson PD, Clarkson PM: Molecular responses of human muscle to eccentric exercise. J Appl Physiol. 2003, 95 (6): 2485-2494.CrossRefPubMed Chen Y-W, Hubal MJ, Hoffman EP, Thompson PD, Clarkson PM: Molecular responses of human muscle to eccentric exercise. J Appl Physiol. 2003, 95 (6): 2485-2494.CrossRefPubMed
29.
go back to reference Trost SG: State of the Art reviews: measurement of physical activity in children and adolescents. American Journal of Lifestyle Medicine. 2007, 1 (4): 299-314. 10.1177/1559827607301686.CrossRef Trost SG: State of the Art reviews: measurement of physical activity in children and adolescents. American Journal of Lifestyle Medicine. 2007, 1 (4): 299-314. 10.1177/1559827607301686.CrossRef
30.
go back to reference Ploeger HE, Takken T, Wilk B, Issenman RM, Sears R, Suri S, Timmons BW: Exercise capacity in pediatric patients with inflammatory bowel disease. J Pediatr. 2011, 158 (5): 814-819. 10.1016/j.jpeds.2010.10.020.CrossRefPubMed Ploeger HE, Takken T, Wilk B, Issenman RM, Sears R, Suri S, Timmons BW: Exercise capacity in pediatric patients with inflammatory bowel disease. J Pediatr. 2011, 158 (5): 814-819. 10.1016/j.jpeds.2010.10.020.CrossRefPubMed
31.
go back to reference Dupont W, Plummer W: Power and sample size calculations: a review and computer program. Control Clin Trials. 1990, 11: 116-128. 10.1016/0197-2456(90)90005-M.CrossRefPubMed Dupont W, Plummer W: Power and sample size calculations: a review and computer program. Control Clin Trials. 1990, 11: 116-128. 10.1016/0197-2456(90)90005-M.CrossRefPubMed
32.
go back to reference Tam CS, Tordjman J, Divoux A, Baur LA, Clement K: Adipose tissue remodeling in children: the link between collagen deposition and age-related adipocyte growth. J Clin Endocrinol Metab. 2012, 97 (4): 1320-1327. 10.1210/jc.2011-2806.CrossRefPubMed Tam CS, Tordjman J, Divoux A, Baur LA, Clement K: Adipose tissue remodeling in children: the link between collagen deposition and age-related adipocyte growth. J Clin Endocrinol Metab. 2012, 97 (4): 1320-1327. 10.1210/jc.2011-2806.CrossRefPubMed
Metadata
Title
Chemokine (C-C motif) Ligand 2 is a potential biomarker of inflammation & physical fitness in obese children: a cross-sectional study
Authors
M Constantine Samaan
Joyce Obeid
Thanh Nguyen
Lehana Thabane
Brian W Timmons
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2013
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/1471-2431-13-47

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