To clarify the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor on whole-body energy metabolism, we treated mice fed a high-fat diet (HFD) with teneligliptin, a clinically available DPP-4 inhibitor. Teneligliptin significantly prevented HFD-induced obesity and obesity-associated metabolic disorders. It also increased oxygen consumption rate and upregulated uncoupling protein 1 (UCP1) expression in both brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT), suggesting that it enhances BAT function. Soluble DPP-4 inhibited β-adrenoreceptor-stimulated UCP1 expression in primary adipocytes, and this inhibition was prevented in the presence of teneligliptin, or an extracellular signal-related kinase inhibitor. These results indicate that soluble DPP-4 inhibits β-adrenoreceptor-stimulated UCP1 induction and that chronic DPP-4 inhibitor treatment may prevent obesity through the activation of BAT function.
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