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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.

Author information

1
Laboratory of Molecular Function of Food Division of Food Science and Biotechnology Graduate School of Agriculture Kyoto University Uji Japan.
2
Research Unit for Physiological Chemistry The Center for the Promotion of Interdisciplinary Education and Research Kyoto University Kyoto Japan.
3
Department of Bioinformatic Engineering Graduate School of Information Science and Technology Osaka University Suita Japan.

Abstract

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.

KEYWORDS:

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

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