, and Are Potential Regulators of Brown Adipose Tissue Development Associated with Obesity-Related Metabolic Dysfunction in Children.

Obesity is already accompanied by adipose tissue (AT) dysfunction and metabolic disease in children and increases the risk of premature death. Due to its energy-dissipating function, brown AT (BAT) has been discussed as being protective against obesity and related metabolic dysfunction. To analyze the molecular processes associated with BAT development, we investigated genome-wide expression profiles in brown and white subcutaneous and perirenal AT samples of children. We identified 39 upregulated and 26 downregulated genes in uncoupling protein 1 (UCP1)-positive compared to UCP1-negative AT samples. We prioritized for genes that had not been characterized regarding a role in BAT biology before and selected cordon-bleu WH2 repeat protein (), mohawk homeobox () and myocilin () for further functional characterization. The siRNA-mediated knockdown of and during brown adipocyte differentiation in vitro resulted in decreased expression, while the inhibition of led to increased expression. Furthermore, , and expression in the subcutaneous AT of children is related to obesity and parameters of AT dysfunction and metabolic disease, such as adipocyte size, leptin levels and HOMA-IR. In conclusion, we identify , and as potential regulators of BAT development and show an association of these genes with early metabolic dysfunction in children.