The dipeptidyl peptidase‐4 ( DPP ‐4) inhibitor teneligliptin enhances brown adipose tissue function, thereby preventing obesity in mice

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 ( UCP 1) 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 UCP 1 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 UCP 1 induction and that chronic DPP ‐4 inhibitor treatment may prevent obesity through the activation of BAT function.