DPP-IV inhibitor anagliptin exerts anti-inflammatory effects on macrophages, adipocytes, and mouse livers by suppressing NF-κB activation

Takanori Shinjo, Yusuke Nakatsu, Misaki Iwashita, Tomomi Sano, Hideyuki Sakoda, Hisamitsu Ishihara, Akifumi Kushiyama, Midori Fujishiro, Toshiaki Fukushima, Yoshihiro Tsuchiya, Hideaki Kamata, Fusanori Nishimura, Tomoichiro Asano

Research output: Contribution to journalArticle

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Abstract

Dipeptidyl peptidase IV (DPPIV) expression in visceral adipose tissue is reportedly increased in obese patients, suggesting an association of DPP-IV with inflammation. In this study, first, lipopolysaccharide (LPS)- or palmitateinduced elevations of inflammatory cytokine mRNA expressions in RAW264.7 macrophages were shown to be significantly suppressed by coincubation with a DPP-IV inhibitor, anagliptin (10 μM), despite low DPP-IV expression in the RAW264.7 cells. Regarding the molecular mechanism, LPS-induced degradation of IκBα and phosphorylations of p65, JNK, and p38, as well as NF- κB and AP-1 promoter activities, were revealed to be suppressed by incubation with anagliptin, indicating suppressive effects of anagliptin on both NF- κB and AP-1 signaling pathways. Anagliptin also acted on 3T3-L1 adipocytes, weakly suppressing the inflammatory cytokine expressions induced by LPS and TNFα. When 3T3-L1 and RAW cells were cocultured and stimulated with LPS, the effects of anagliptin on the suppression of cytokine expressions in 3T3-L1 adipocytes were more marked and became evident at the 10 μM concentration. Anti-inflammatory effects of anagliptin were also observed in vivo on the elevated hepatic and adipose expressions and serum concentrations of inflammatory cytokines in association with the suppression of hepatic NF- κB transcriptional activity in LPS-infused mice. Taking these observations together, the anti-inflammatory properties of anagliptin may be beneficial in terms of preventing exacerbation of diabetes and cardiovascular events.

Original languageEnglish
Pages (from-to)E214-E223
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume309
Issue number3
DOIs
Publication statusPublished - Aug 5 2015

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Adipocytes
Anti-Inflammatory Agents
Macrophages
Lipopolysaccharides
Liver
Cytokines
Transcription Factor AP-1
3T3-L1 Cells
Dipeptidyl Peptidase 4
Intra-Abdominal Fat
anagliptin
Phosphorylation
Inflammation
Messenger RNA
Serum

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

DPP-IV inhibitor anagliptin exerts anti-inflammatory effects on macrophages, adipocytes, and mouse livers by suppressing NF-κB activation. / Shinjo, Takanori; Nakatsu, Yusuke; Iwashita, Misaki; Sano, Tomomi; Sakoda, Hideyuki; Ishihara, Hisamitsu; Kushiyama, Akifumi; Fujishiro, Midori; Fukushima, Toshiaki; Tsuchiya, Yoshihiro; Kamata, Hideaki; Nishimura, Fusanori; Asano, Tomoichiro.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 309, No. 3, 05.08.2015, p. E214-E223.

Research output: Contribution to journalArticle

Shinjo, Takanori ; Nakatsu, Yusuke ; Iwashita, Misaki ; Sano, Tomomi ; Sakoda, Hideyuki ; Ishihara, Hisamitsu ; Kushiyama, Akifumi ; Fujishiro, Midori ; Fukushima, Toshiaki ; Tsuchiya, Yoshihiro ; Kamata, Hideaki ; Nishimura, Fusanori ; Asano, Tomoichiro. / DPP-IV inhibitor anagliptin exerts anti-inflammatory effects on macrophages, adipocytes, and mouse livers by suppressing NF-κB activation. In: American Journal of Physiology - Endocrinology and Metabolism. 2015 ; Vol. 309, No. 3. pp. E214-E223.
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AU - Sakoda, Hideyuki

AU - Ishihara, Hisamitsu

AU - Kushiyama, Akifumi

AU - Fujishiro, Midori

AU - Fukushima, Toshiaki

AU - Tsuchiya, Yoshihiro

AU - Kamata, Hideaki

AU - Nishimura, Fusanori

AU - Asano, Tomoichiro

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