Adipose Tissue Remodeling in Children: The Link between Collagen Deposition and Age-Related Adipocyte Growth

Context: 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. Main Outcome Measures: 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. Conclusion: 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. (J Clin Endocrinol Metab 97: 1320-1327, 2012)