Abstract

Abstract Disclosure: Y. Cui: None. X. Zhang: None. L. You: None. H. Zhong: None. X. Cui: None. C. Ji: None. Obesity and its associated chronic diseases, such as type 2 diabetes mellitus, hypertension, and coronary artery disease, afflicting adults and children globally. PSMB9, a proteolytic subunit of the immunoproteasome that shapes the repertoire of antigenic peptides, is hypothesized to be associated with obesity. To investigate this association, we examined PSMB9 expression in primary mature adipocytes from obese and normal individuals. LC-MS/MS-PRM was used to quantify PSMB9 content in primary mature adipocytes, revealing a negative correlation between PSMB9 content and obesity while positively correlated with high-density lipoprotein levels. Furthermore, we examined the effect of PSMB9 on human preadipocyte differentiation. During the early stages of differentiation, the expression of PSMB9 was at its highest level, decreasing as preadipocytes matured. Overexpression of PSMB9 significantly inhibited preadipocyte differentiation, resulting in reduced lipid droplets and decreased expression levels of classical differentiation markers such as FABP4, C/EBPα, and PPARγ. These findings suggest that PSMB9 could be a potential therapeutic target for preventing and treating obesity and metabolic disorders. In conclusion, our study provides insights into the role of the immunoproteasome in obesity and highlights the importance of further exploration of this pathway. Presentation: Saturday, June 17, 2023

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