KBN2201 Attenuates High-Fat Diet-Induced Adipose Tissue Expansion and Body Weight Gain in Male Mice.

Obesity is characterized by pathological adipose tissue expansion and dysregulated energy homeostasis. In this study, we examined whether KBN2201 attenuates high-fat diet (HFD)-induced obesity-associated phenotypes and whether these effects are accompanied by changes in appetite-regulatory markers. C57BL/6J mice were fed a normal chow diet or HFD and orally administered vehicle or KBN2201 (20 mg/kg/day) for 12 weeks. In male mice, KBN2201 reduced HFD-induced body weight gain, adipose tissue accumulation, and adipocyte hypertrophy. KBN2201 was also associated with lower cage-level caloric intake under HFD-fed conditions. In epididymal white adipose tissue (eWAT), KBN2201 suppressed Srebf1 expression and reduced HFD-induced increases in Tnf and Tgfb1 expression. In the colon, KBN2201 further increased Pyy mRNA expression, and a positive mRNA-level association was observed between colonic Pyy and Npy2r expression in NTS-containing brainstem tissue. Behavioral analyses provided no evidence of overt locomotor suppression under the present experimental conditions. These findings suggest that KBN2201 attenuates HFD-induced obesity-associated phenotypes in male mice, accompanied by a lower cage-level food intake pattern, reduced adipose tissue expansion, and changes in the expression of colonic Pyy and NTS-containing brainstem Npy2r.