HTR2B Upregulation induces Adipose Aging and Is Attenuated by Hederagenin

Adipose tissue, as a key organ regulating systemic metabolism, undergoes functional disorders with aging, which is a significant inducer of obesity and non-alcoholic fatty liver disease. The 5-HT2B receptor (HTR2B) has been identified to be closely associated with the development of obesity-induced insulin resistance, but its role in adipose tissue aging remains unclear. In this study, we found that the expression of HTR2B was significantly increased in white adipose tissue of aged mice, accompanied by metabolic abnormalities, which was also supported by GEO dataset analysis. Subsequent experiments showed that transfection with HTR2B knockdown genes significantly reduced intracellular calcium ion concentration. Moderate targeted reduction of 5-HT2B expression via the traditional Chinese medicine component Hederagenin could notably alleviate oxidative damage, along with decreased lipid droplet accumulation. These results support the hypothesis that inhibiting HTR2B expression in adipocytes may represent a therapeutic approach for age-related obesity.