Brown adipose tissue (BAT) plays a critical role in energy homeostasis by converting stored energy into heat through thermogenesis. Gemigliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has shown potential in regulating glucose metabolism, energy expenditure, and BAT thermogenesis. This study investigated the effects of gemigliptin on thermogenesis and metabolic regulation, with a focus on its role in activating uncoupling protein 1 (UCP1).

Methods All animal experiment used male C57BL/6J mice at 6 weeks of ages. The energy expenditure (EE) and counts of ambulatory physical activity (rearing, activity) in mice were performed at 18–19 weeks of age and analyzed using indirect calorimetry (InAnlyzer, MEDIKORS). Tissue samples were dissected from mice at 20 weeks of ages, fixed, processed and embedded in paraffin. Total RNA was isolated using TRIzol reagent and cDNA was prepared from total RNA using M-MLV reverse transcription and oligo-dT primers. The resultant cDNA was amplified using Rotor-Gene 6000 realtime rotary analysis software. Real –time OCR was performed in triplicate with individual time-matched using QuantiTectTM SYBR® Green PCR Master Mix.

Gemigliptin treatment significantly increased EE in mice during both the night and day cycles compared to controls, as demonstrated by the area under the curve (AUC) analysis. Locomotor activity, particularly during the night, was significantly higher in gemigliptin-treated mice, while rearing activity showed no noticeable differences. The BAT of gemigliptin treated mice showed the expression of UCP1 and other genes associated with BAT thermogenesis was higher than control mice.

Our study suggested that gemigliptin might be a therapeutic agent for metabolic disorder through effects on BAT thermogenesis.