UCLA

In the United States, approximately a third of the population is affected by obesity, with exercise and dietary modifications implemented as the traditional methods of combatting metabolic-related diseases. We identified ubiquitin-like modifier FAT10 as a novel protein significantly correlated with adiposity. Despite the scientific literature describing FAT10 in various inflammation-driven disorders and types of cancers, the mechanism by which FAT10 regulates metabolic pathways in white and brown adipose tissue is not well understood. Here, we demonstrate the dynamic expression of FAT10 in adipose tissue and show adipose-specific FAT10 gain-of-expression mice mitigates weight gain by altering lipid metabolism and energy homeostasis. Within white adipose depots, small adipocytes present in significantly higher numbers with FAT10 overexpression compared to controls, while brown adipose depots present with a decrease in lipid content. Adipose tissue overexpression of FAT10 induces lipolysis and fuels catabolic processes such as fatty acid oxidation and UCP1-dependent non-shivering thermogenesis. Our findings indicate FAT10 plays a diverse and critical role in both white and brown adipose tissue regarding the regulation of lipolysis, fatty acid oxidation, and UCP1-dependent thermogenesis, suggesting a potential therapeutic target to combat obesity and metabolic-associated diseases.