KBN2202 Suppresses Adipose Tissue Expansion in a High-Fat Diet-Induced Obesity Mouse Model

Obesity treatments increasingly target multiple pathways beyond appetite suppression. We evaluated KBN2202, a salicylate-derived small molecule, in a high-fat diet (60% kcal) mouse model using female and male C57BL/6J mice treated for 8 weeks with oral KBN2202 (20 mg/kg/day) or matched-volume vehicle (1% DMSO/PBS). Body weight and food intake were tracked weekly; serum hormones/cytokines, adipose tissue histology, and open-field behavior were assessed at study end. KBN2202 significantly reduced peri-ovarian gonadal white adipose tissue (gWAT) mass and adipocyte size in females without altering overall body weight. Circulating glucagon-like peptide-1 (GLP-1) increased, uncoupling protein 1 (UCP1) in gWAT showed a non-significant upward trend, and serum TNF-α was selectively decreased, while MCP-1 and IL-1β were unchanged. Despite higher apparent food intake, locomotor activity was unaltered and anxiety-like behavior was reduced. Male mice did not show comparable adipose effects. These findings indicate depot-specific, peripheral modulation of adipose remodeling, hormonal balance, and inflammatory tone by KBN2202, supporting its further investigation as an adipose-targeted metabolic modulator complementary to incretin-based therapies.