KBN2202 Suppresses Gonadal White Adipose Tissue Expansion in Female Mice Fed a High-Fat Diet

TL;DR

A new molecule called KBN2202 reduces fat tissue growth in female mice on a high-fat diet without affecting body weight.

Contribution

KBN2202 shows depot-specific effects on adipose tissue and inflammation in female mice.

Findings

KBN2202 reduced peri-ovarian white adipose tissue mass and adipocyte size in female mice.

KBN2202 increased circulating GLP-1 and showed a trend in increasing UCP1 in gWAT.

KBN2202 selectively decreased serum TNF-α without affecting other inflammatory markers.

Abstract

Obesity treatments increasingly target multiple pathways beyond appetite suppression. We evaluated KBN2202, a salicylate-derived small molecule, in a high-fat diet (60% kcal from fat) mouse model using female and male C57BL/6J mice treated for 8 weeks with oral KBN2202 (20 mg/kg/day) or a matched-volume vehicle (1% DMSO/PBS). Body weight was recorded weekly, and food intake was measured daily; serum hormones and cytokines, adipose tissue histology, and open-field behavior were assessed at the end of the study. Under our experimental conditions, HFD increased body weight and gonadal white adipose tissue (gWAT)/brown adipose tissue (BAT) mass in females, whereas males showed only modest HFD-associated weight gain and did not develop a clear obesity phenotype. KBN2202 significantly reduced peri-ovarian gWAT mass and adipocyte size without altering overall body weight. In females, 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. 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.

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