title: Metabolic endotoxaemia in childhood obesity.
abstract: BACKGROUND
  Childhood obesity is associated with chronic low-grade inflammation considered as a precursor to metabolic disease; however, the underlying mechanisms for this remain unclear. Studies in adults have implicated gut derived gram-negative bacterial fragments known as lipopolysaccharide or endotoxin, activating the inflammatory response, whilst the importance in childhood obesity is unclear. The aim of this research is to understand the relationship between circulating endotoxin in childhood obesity, and its' association with inflammatory and cardiovascular (CV) injury biomarkers.
  
  
  METHODS
  Fasted blood was obtained from children with varying degrees of obesity (age: 13.9 ± 2.3Yr; BMI: 35.1 ± 5.2 Kg/m(2); n = 60). Multiplex CVD biomarker immunoassays were used to determine systemic levels of inflammatory and vascular injury biomarkers, such as tumour necrosis factor-α (TNF-α), interleukin (IL-) 1β, 6, 8 and 10, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule type-1 (sICAM-1), matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO) and vascular endothelial growth factor (VEGF) as well as endotoxin levels.
  
  
  RESULTS
  Endotoxin levels demonstrated a significant and positive correlation with the markers for inflammation, vascular injury and atherogenesis (TNF-α: r(2) = 0.077, p < 0.05; PAI-1: r(2) = 0.215, p < 0.01; sICAM-1: r(2) = 0.159, p < 0.01; MMP-9: r(2) = 0.159, p < 0.01; MPO: r(2) = 0.07, p < 0.05; VEGF: r(2) = 0.161, p < 0.01). Males demonstrated significantly higher circulating endotoxin than females (Males: 9.63 ± 5.34 EU/ml; p = 0.004; Females: 5.56 ± 4.06 EU/ml; n = 60) in these BMI and age-matched cohorts.
  
  
  CONCLUSIONS
  The present study demonstrates for the first time a significant association between circulating endotoxin and biomarkers of metabolic risk in children as young as 11 years. Thus, endotoxin-mediated sub-clinical inflammation during childhood obesity may be a key contributor to T2DM and CVD development later in life.
authors.affiliation: Division of Biomedical sciences,, Warwick Medical School, University of Warwick, UHCW Trust, Clifford Bridge Road, Walsgrave, Coventry CV2 2DX UK.
authors.forename: Madhusudhan C
authors.initials: MC
authors.lastname: Varma
authors.affiliation: Division of Biomedical sciences,, Warwick Medical School, University of Warwick, UHCW Trust, Clifford Bridge Road, Walsgrave, Coventry CV2 2DX UK.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Kusminski
authors.affiliation: Division of Biomedical sciences,, Warwick Medical School, University of Warwick, UHCW Trust, Clifford Bridge Road, Walsgrave, Coventry CV2 2DX UK.
authors.forename: Sahar
authors.initials: S
authors.lastname: Azharian
authors.affiliation: Department of Medical Sciences & Rehabilitation, IRCCS Istituto Auxologico Italiano, Via Ariosto 13, 20145 Milan, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Gilardini
authors.affiliation: Division of Biomedical sciences,, Warwick Medical School, University of Warwick, UHCW Trust, Clifford Bridge Road, Walsgrave, Coventry CV2 2DX UK.
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Medical Sciences & Rehabilitation, IRCCS Istituto Auxologico Italiano, Via Ariosto 13, 20145 Milan, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Invitti
authors.affiliation: Division of Biomedical sciences,, Warwick Medical School, University of Warwick, UHCW Trust, Clifford Bridge Road, Walsgrave, Coventry CV2 2DX UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: McTernan
keywords: Cardiovascular injury markers; Childhood obesity; Endotoxin; Insulin resistance
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