title: Adipose tissue remodeling in children: the link between collagen deposition and age-related adipocyte growth.
abstract: BACKGROUND
  Extracellular matrix (ECM) remodeling is essential for adipose tissue growth and expansion in high fat-fed mice, and there is evidence of fibrosis in adipose tissue in human obesity.
  
  
  OBJECTIVE
  The aim of the study was to explore the role of ECM remodeling in adipose tissue in healthy, growing children. RESEARCH DESIGN, SETTING, AND PARTICIPANTS: Abdominal sc adipose biopsies were obtained from 65 otherwise healthy children [57 boys; age, 5.3 ± 3.8 yr (mean ± sd)] having elective surgery (cross-sectional study). Twenty percent of the participants were classified as overweight/obese based on body mass index (BMI) z score.
  
  
  METHODS
  We examined collagen (total and pericellular), HAM56+ macrophages, CD206+ M2 phenotype macrophages, and CD3+ T cells measured by immunohistochemistry and ECM gene expression markers.
  
  
  RESULTS
  Overweight children had significantly less total collagen compared to normal weight children (median, 3.4 vs. 9.1%; P = 0.001). However, collagen areas were not positive for COL6 and showed little evidence of collagen surrounding adipocytes. Fat cell size was negatively correlated with the percentage of total (r = -0.398; P = 0.003) and pericellular collagen (r = -0.462; P < 0.001) but positively correlated with HAM56+ macrophages (r = 0.541; P < 0.001). The percentage of total collagen was inversely associated with BMI z score (r = -0.345; P = 0.01) and age (r = -0.348; P = 0.005), with older (>11 yr old) children in the top BMI z tertile having less collagen (3.8%) than younger (2-5 yr old) children in the bottom BMI z tertile (12.6%). Adipose tissue in overweight children showed little evidence of crown-like structures or T cells.
  
  
  CONCLUSIONS
  In healthy, growing children, increased collagen in adipose tissue is associated with decreased fat cell size and BMI z score and increased M2+ phenotype macrophages, suggesting dynamic interaction between ECM remodeling and immune cells even at an early age.
authors.affiliation: Institue of Endocrinology and Diabetes, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia. charmaine.tam@pbrc.edu
authors.forename: Charmaine S
authors.initials: CS
authors.lastname: Tam
authors.forename: Joan
authors.initials: J
authors.lastname: Tordjman
authors.forename: Adeline
authors.initials: A
authors.lastname: Divoux
authors.forename: Louise A
authors.initials: LA
authors.lastname: Baur
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
mesh_terms: D050156:Adipogenesis; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015992:Body Mass Index; D002452:Cell Count; D048429:Cell Size; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D015331:Cohort Studies; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D009517:New South Wales; D050177:Overweight / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D020033:Protein Isoforms; D003094:Collagen