Changes in CIDEA expression associate with adipocytes size and functionality in adolescent obese girls

About 20% of youth are obese with higher risk for cardiovascular disease and type 2 diabetes (T2D). We have recently reported that in obese adolescents altered pattern of fat distribution is associated with insulin resistance and T2D. In particular, the high ratio of visceral AT depot (VAT) to abdominal subcutaneous AT depot (SAT) (high VAT/(VAT+SAT)) was associated with a metabolically unhealthy phenotype with high risk for insulin resistance and T2D. CIDEA (Cell death inducing DNA fragmentation factor-alpha-like A) is a member of CIDE family and it is not only involved in the promotion of cell death and DNA fragmentation but it also plays critical roles in the lipid droplets formation and growth. Here we demonstrated in abdominal SAT from adolescent obese girls with high VAT/(VAT+SAT) a significant reduction of CIDEA expression associated with an increase in fasting insulin, serum FFA and consequent insulin resistance. We also demonstrated a direct correlation between CIDEA expression and fraction of large cells and an inverse correlation with small adipocytes number and pre-adipocytes proliferation. After gaining weight, we observed an increase in adipocytes cell diameter but a decrease in CIDEA expression, and the transcriptomic analysis showed a gene profile linked to adipocyte dysfunction. Together, these data suggested that in subjects with high VAT/(VAT+SAT) decreased CIDEA expression is associated with an increase in adipocyte cell sizing and consecutive insulin resistance. Overall design: Human Abdominal Subcutaneous Adipose tissue (SAT) mRNA profiles of 18 obese subjects and SAT mRNA profile of 4 subjects returned after gaining weight (sequencing using Illumina Hi-Seq4000).