The Polymer Society of Korea

이수호 (한양대학교)

이동윤 (한양대학교)

Obesity-induced chronic inflammation in white adipose tissue (WAT) is critically driven by the overexpression of the receptor for advanced glycation end-products (RAGE). We hypothesized that RAGE activation accelerates obesity by promoting AMP-activated protein kinase (AMPK) dephosphorylation and suppressing thermogenesis. To address this, we developed a novel peptide antagonist, RBP-8. RBP-8 selectively bound to RAGE, suppressing its expression while upregulating Sirtuin-1 (SIRT1), a key AMPK regulator. Furthermore, RBP-8 induced white adipocyte browning, characterized by reduced lipid droplet size, enhanced mitochondrial biogenesis, and brown adipocyte-specific gene activation. In a diet-induced obesity mouse model, RBP-8 reduced body weight by approximately 5% compared to high-fat diet controls. These findings indicate that RAGE inhibition via RBP-8 promotes thermogenesis, representing a promising therapeutic strategy for obesity.