title: Chemokine (C-C motif) Ligand 2 is a potential biomarker of inflammation & physical fitness in obese children: a cross-sectional study.
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.
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, McMaster Children’s Hospital, McMaster University, 1280 Main Street West, HSC-3A57, Hamilton, Ontario L8S 4K1, Canada. samaanc@mcmaster.ca
authors.forename: M Constantine
authors.initials: MC
authors.lastname: Samaan
authors.forename: Joyce
authors.initials: J
authors.lastname: Obeid
authors.forename: Thanh
authors.initials: T
authors.lastname: Nguyen
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.forename: Brian W
authors.initials: BW
authors.lastname: Timmons
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood*; D002648:Child; D003430:Cross-Sectional Studies; D005080:Exercise Test; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000209:etiology; D008297:Male; D063766:Pediatric Obesity / Q000097:blood* / Q000503:physiopathology; D010809:Physical Fitness / Q000502:physiology*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2
references.citation: Arch Physiol Biochem. 2009 Feb;115(1):22-7
references.pmid: 19267279
references.citation: Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1300-10
references.pmid: 19336660
references.citation: Circulation. 2008 Apr 1;117(13):1649-57
references.pmid: 18347211
references.citation: Pediatrics. 2006 Sep;118(3):e594-601
references.pmid: 16950951
references.citation: J Clin Invest. 2003 Dec;112(12):1785-8
references.pmid: 14679172
references.citation: J Pediatr. 2011 May;158(5):814-9
references.pmid: 21146188
references.citation: J Clin Endocrinol Metab. 2012 Apr;97(4):1320-7
references.pmid: 22259057
references.citation: J Appl Physiol (1985). 2003 Dec;95(6):2485-94
references.pmid: 12937035
references.citation: J Biol Chem. 2006 Sep 8;281(36):26602-14
references.pmid: 16809344
references.citation: J Clin Invest. 2003 Dec;112(12):1796-808
references.pmid: 14679176
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7265-70
references.pmid: 12756299
references.citation: Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6953-7
references.pmid: 1379728
references.citation: J Pediatr. 2007 Jan;150(1):12-17.e2
references.pmid: 17188605
references.citation: Diabetologia. 2009 May;52(5):972-81
references.pmid: 19277603
references.citation: Diabetes. 2012 Aug;61(8):1986-93
references.pmid: 22688341
references.citation: Int J Pediatr Obes. 2006;1(1):11-25
references.pmid: 17902211
references.citation: Metabolism. 2006 Sep;55(9):1232-8
references.pmid: 16919544
references.citation: Control Clin Trials. 1990 Apr;11(2):116-28
references.pmid: 2161310
references.citation: Lancet. 2001 Feb 17;357(9255):505-8
references.pmid: 11229668
references.citation: Sleep. 2008 May;31(5):619-26
references.pmid: 18517032
references.citation: Am J Clin Nutr. 2010 Nov;92(5):1257-64
references.pmid: 20861173
references.citation: Lancet. 2002 Aug 10;360(9331):473-82
references.pmid: 12241736
references.citation: Metabolism. 2011 Apr;60(4):445-52
references.pmid: 20494373
references.citation: Front Biosci (Landmark Ed). 2009 Jan 01;14:540-51
references.pmid: 19273084
references.citation: Postgrad Med J. 2006 Jul;82(969):429-37
references.pmid: 16822919
references.citation: Int J Obes (Lond). 2006 Sep;30(9):1347-55
references.pmid: 16534530
references.citation: Sleep Med. 2011 Dec;12(10):997-1002
references.pmid: 22036601
references.citation: Circulation. 2005 Apr 19;111(15):1999-2012
references.pmid: 15837955
references.citation: J Pediatr. 2010 Nov;157(5):815-20
references.pmid: 20955852