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

• Published in: International journal of molecular sciences 2023-02, Vol.24 (4), p.3085
• Main Authors: Abdul Majeed, Sarah, Dunzendorfer, Helene, Weiner, Juliane, Heiker, John T, Kiess, Wieland, Körner, Antje, Landgraf, Kathrin
• Format: Article
• Language: English
• Subjects: adipocyte differentiation; Adipocytes; Adipocytes, Brown - metabolism; Adipose tissue; Adipose tissue (brown); Adipose Tissue, Brown - metabolism; Adipose Tissue, White - metabolism; Body fat; brown adipose tissue; Child; Children; Cobl protein; Cold; Cytoskeletal Proteins - metabolism; Eye Proteins - metabolism; Gene expression; Genes; Genomes; Homeobox; Humans; Leptin; Metabolic disorders; Metabolism; Mitochondria; Obesity; Obesity - metabolism; Proteins; siRNA; Stem cells; Thermogenesis - genetics; Uncoupling protein 1; Uncoupling Protein 1 - metabolism; white adipose tissue
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24043085

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.