Background: Accumulation of fat mass in the development of obesity may result from hypertrophy and/or hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in adults. However, the onset and mechanisms of AT dysfunction are not entirely understood.
Objective and hypotheses: We assessed composition, function, lipolysis, and inflammation in 171 AT samples from lean and obese children and adolescents (aged 0 18 years) to evaluate early alterations in AT biology with the development of obesity in children.
Results: In normal lean children, both adipocyte size (R=0.62) and number (R=0.76) gradually increased with age. Beginning in early childhood, obese children have significantly enlarged adipocytes (by 17%) compared to lean children, and adipocyte number is 2.6-fold increased. The proliferation rate of stromal vascular cells is threefold enhanced in obese children, whereas the differentiation potential remained unchanged. These alterations in AT composition in obese children were accompanied by increased macrophage infiltration and formation of crown-like structures. Macrophage infiltration was associated with age (R=0.23), BMISDS (R=0.35), and adipocyte size (R=0.41) in univariate analyses, but was largely dependent on adipocyte size in multivariate analyses. Furthermore, expression of extracellular matrix marker genes (COL6A1 and SPARC) was upregulated in AT of obese children indicating the early development of AT fibrosis. Finally, we detected a significant decrease in basal lipolytic activity up to ~60% in obese children.
Conclusion: In summary, we showed that adipocyte hypertrophy and hyperplasia is linked to functional metabolic impairment and increased inflammation in AT from obese children thereby providing evidence that obesity-associated AT dysfunction develops in early childhood.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology