Trim21 Regulates the Postnatal Development and Thermogenesis of Brown Adipose Tissue

Brown adipose tissue undergoes rapid postnatal development to mature and plays a crucial role in thermoregulation and energy expenditure, which protects against cold and obesity. Herein, it is shown that the expression of Trim21 mRNA level of interscapular brown adipose tissue elevates after birth, and peaks at P14 (postnatal day 14). Trim21 depletion severely impairs the maturation of interscapular brown adipose tissue, decreases the expression of a series of thermogenic genes, and reduces energy expenditure. Consistently, the loss of Trim21 also leads to a suppression of white adipose tissue "browning", in response to cold exposure and a beta-adrenergic agonist, CL316,243. In addition, Trim21-/- mice are more prone to high-fat diet-induced obesity compared with the control littermates. Taken together, the study for the first time reveals a critical role of Trim21 in regulating iBAT postnatal development and thermogenesis. Trim21 is dominantly expressed in the iBAT (interscapular brown adipose tissue). Trim21 depletion results in the "whitening" phenotype of iBAT (lipid droplets accumulation), reduces energy expenditure and iBAT-mediated adaptive thermogenesis, promotes high-fat diet-induced obesity. The findings uncover critical roles of Trim21 in regulating iBAT postnatal development and thermogenesis, and provide a new perspective for combating obesity and its comorbidities.image