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FEBS Open Bio. 2018 Sep 19;8(11):1782-1793. doi: 10.1002/2211-5463.12498. eCollection 2018 Nov.

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

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Laboratory of Molecular Function of Food Division of Food Science and Biotechnology Graduate School of Agriculture Kyoto University Uji Japan.
Research Unit for Physiological Chemistry The Center for the Promotion of Interdisciplinary Education and Research Kyoto University Kyoto Japan.
Department of Bioinformatic Engineering Graduate School of Information Science and Technology Osaka University Suita Japan.


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.


UCP1; beige adipocytes; brown adipocytes; dipeptidyl peptidase‐4; obesity; teneligliptin

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