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

Kenichiro Takeda, Honami Sawazaki, Haruya Takahashi, Yu Sheng Yeh, Huei Fen Jheng, Wataru Nomura, Takeshi Ara, Nobuyuki Takahashi, Shigeto Seno, Naoki Osato, Hideo Matsuda, Teruo Kawada, Tsuyoshi Goto

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1782-1793
Number of pages12
JournalFEBS Open Bio
Volume8
Issue number11
DOIs
Publication statusPublished - 2018 Nov
Externally publishedYes

Keywords

  • UCP1
  • beige adipocytes
  • brown adipocytes
  • dipeptidyl peptidase-4
  • obesity
  • teneligliptin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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