Metabolic endotoxaemia in childhood obesity

Madhusudhan C. Varma, Christine M. Kusminski, Sahar Azharian, Luisa Gilardini, Sudhesh Kumar, Cecilia Invitti, Philip G. McTernan

Research output: Contribution to journalArticle

14 Scopus citations

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/m2; 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: r2 = 0.077, p < 0.05; PAI-1: r2 = 0.215, p < 0.01; sICAM-1: r2 = 0.159, p < 0.01; MMP-9: r2 = 0.159, p < 0.01; MPO: r2 = 0.07, p < 0.05; VEGF: r2 = 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. Conclusion: 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.

Original languageEnglish (US)
Article number3
JournalBMC Obesity
Volume3
Issue number1
DOIs
StatePublished - 2016

Keywords

  • Cardiovascular injury markers
  • Childhood obesity
  • Endotoxin
  • Insulin resistance

ASJC Scopus subject areas

  • Epidemiology
  • Endocrinology, Diabetes and Metabolism
  • Physical Therapy, Sports Therapy and Rehabilitation
  • Health Policy
  • Public Health, Environmental and Occupational Health

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  • Cite this

    Varma, M. C., Kusminski, C. M., Azharian, S., Gilardini, L., Kumar, S., Invitti, C., & McTernan, P. G. (2016). Metabolic endotoxaemia in childhood obesity. BMC Obesity, 3(1), [3]. https://doi.org/10.1186/s40608-016-0083-7