title: The impact of childhood obesity on inflammation, innate immune cell frequency, and metabolic microRNA expression.
abstract: BACKGROUND
  Obesity is characterized by chronic inflammation, immune dysregulation, and alteration of gene expression, associated with type 2 diabetes mellitus and cardiovascular disease. The degree to which these changes occur in childhood obesity is not fully defined.
  
  
  OBJECTIVE
  The aim was to investigate the effect of childhood obesity on immune cell frequency, macrophage activation, cytokine production, and specific regulators of metabolic gene expression. Profiling was performed on peripheral blood from 29 obese and 20 nonobese children using real-time PCR, ELISA, and flow cytometry.
  
  
  RESULTS
  Fasting glucose was similar in both groups, but there was a higher degree of insulin resistance in obese subjects (homeostasis model of assessment for insulin resistance, 4.8 vs 0.84; P < .001). Soluble CD163, a marker of macrophage polarization to a proinflammatory profile, was elevated in the obese compared to nonobese children (135 vs 105 ng/mL; P = .03). Invariant natural killer T cells were reduced in the obese children (CD3 T cells, 0.31 vs 0.53%; P = .001). Cytokine profiling revealed significantly elevated TNF-α (6.7 vs 5.1 pg/mL; P = .01) and leptin (1186 vs 432 pg/mL; P < .001) and reduced adiponectin (884 vs 1321 pg/mL; P = .001) in obese compared to nonobese children. Stimulation of peripheral blood mononuclear cells from obese children resulted in higher levels of IL-1β (2100 vs 1500 pg/mL; P = .018). There was a 4-fold increase in expression of microRNA33a (P = .001) and a 3-fold increase in microRNA33b (P = .017) in obese children.
  
  
  CONCLUSIONS
  Childhood obesity is associated with changes in immune cell frequency, inflammatory environment, and regulation of metabolic gene expression. These changes have been causally linked to the onset of metabolic disease in adulthood and suggest the future trajectory of obese children to the development of type 2 diabetes mellitus and premature cardiovascular disease.
authors.affiliation: Obesity Immunology Group (E.C., A.E.H., M.C., G.G., J.O., D.O.), Education and Research Centre, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland; National Children's Research Centre (E.C., A.E.H.), and Department of Diabetes and Endocrinology (E.C., D.C.), Our Lady's Children's Hospital Crumlin, Dublin 12, Ireland; Department of Endocrinology (J.O., D.O.), St Columcille's Hospital, Loughlinstown, Dublin, Ireland; and Trinity Biomedical Sciences Institute (N.F., L.A.O.), School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Eirin
authors.initials: E
authors.lastname: Carolan
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Hogan
authors.forename: Michelle
authors.initials: M
authors.lastname: Corrigan
authors.forename: Gadintshware
authors.initials: G
authors.lastname: Gaotswe
authors.forename: Jean
authors.initials: J
authors.lastname: O'Connell
authors.forename: Niamh
authors.initials: N
authors.lastname: Foley
authors.forename: Luke A
authors.initials: LA
authors.lastname: O'Neill
authors.forename: Declan
authors.initials: D
authors.lastname: Cody
authors.forename: Donal
authors.initials: D
authors.lastname: O'Shea
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000276:immunology*; D007333:Insulin Resistance / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000166:cytology*; D063766:Pediatric Obesity / Q000150:complications / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000097:blood; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D035683:MicroRNAs; D011956:Receptors, Cell Surface