Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus

Masato Furuhashi, Shinya Hiramitsu, Tomohiro Mita, Takahiro Fuseya, Shutaro Ishimura, Akina Omori, Megumi Matsumoto, Yuki Watanabe, Kyoko Hoshina, Marenao Tanaka, Norihito Moniwa, Hideaki Yoshida, Junichi Ishii, Tetsuji Miura

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Fatty acid binding protein 4 (FABP4), also known as adipocyte FABP or aP2, is secreted from adipocytes in association with lipolysis as a novel adipokine, and elevated serum FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the modulation of serum FABP4 level by therapeutic drugs. Sitagliptin (50 mg/day), a dipeptidyl peptidase 4 (DPP-4) inhibitor that increases glucagon-like peptide 1 (GLP-1), was administered to patients with type 2 diabetes (n = 24) for 12 weeks. Treatment with sitagliptin decreased serum FABP4 concentration by 19.7% (17.8 ± 1.8 vs. 14.3 ± 1.5 ng/ml, P<0.001) and hemoglobin A1c without significant changes in adiposity or lipid variables. In 3T3-L1 adipocytes, sitagliptin or exendin-4, a GLP-1 receptor agonist, had no effect on short-term (2 h) secretion of FABP4. However, gene expression and long-term (24 h) secretion of FABP4 were significantly reduced by sitagliptin, which was not mimicked by exendin-4. Treatment with recombinant DPP-4 increased gene expression and long-term secretion of FABP4, and the effects were cancelled by sitagliptin. Furthermore, knockdown of DPP-4 in 3T3-L1 adipocytes decreased gene expression and long-term secretion of FABP4. In conclusion, sitagliptin decreases serum FABP4 level, at least in part, via reduction in the expression and consecutive secretion of FABP4 in adipocytes by direct inhibition of DPP-4.

Original languageEnglish
Pages (from-to)2372-2380
Number of pages9
JournalJournal of Lipid Research
Volume56
Issue number12
DOIs
Publication statusPublished - 01-12-2015

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Dipeptidyl-Peptidase IV Inhibitors
Fatty Acid-Binding Proteins
Medical problems
Type 2 Diabetes Mellitus
Blood Proteins
Adipocytes
Dipeptidyl Peptidase 4
Gene expression
Gene Expression
Sitagliptin Phosphate
Adipokines
Glucagon-Like Peptide 1
Lipolysis
Adiposity
Insulin Resistance
Atherosclerosis
Hemoglobins
Therapeutics
Obesity
Modulation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Furuhashi, M., Hiramitsu, S., Mita, T., Fuseya, T., Ishimura, S., Omori, A., ... Miura, T. (2015). Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus. Journal of Lipid Research, 56(12), 2372-2380. https://doi.org/10.1194/jlr.M059469
Furuhashi, Masato ; Hiramitsu, Shinya ; Mita, Tomohiro ; Fuseya, Takahiro ; Ishimura, Shutaro ; Omori, Akina ; Matsumoto, Megumi ; Watanabe, Yuki ; Hoshina, Kyoko ; Tanaka, Marenao ; Moniwa, Norihito ; Yoshida, Hideaki ; Ishii, Junichi ; Miura, Tetsuji. / Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus. In: Journal of Lipid Research. 2015 ; Vol. 56, No. 12. pp. 2372-2380.
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Furuhashi, M, Hiramitsu, S, Mita, T, Fuseya, T, Ishimura, S, Omori, A, Matsumoto, M, Watanabe, Y, Hoshina, K, Tanaka, M, Moniwa, N, Yoshida, H, Ishii, J & Miura, T 2015, 'Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus', Journal of Lipid Research, vol. 56, no. 12, pp. 2372-2380. https://doi.org/10.1194/jlr.M059469

Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus. / Furuhashi, Masato; Hiramitsu, Shinya; Mita, Tomohiro; Fuseya, Takahiro; Ishimura, Shutaro; Omori, Akina; Matsumoto, Megumi; Watanabe, Yuki; Hoshina, Kyoko; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hideaki; Ishii, Junichi; Miura, Tetsuji.

In: Journal of Lipid Research, Vol. 56, No. 12, 01.12.2015, p. 2372-2380.

Research output: Contribution to journalArticle

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T1 - Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus

AU - Furuhashi, Masato

AU - Hiramitsu, Shinya

AU - Mita, Tomohiro

AU - Fuseya, Takahiro

AU - Ishimura, Shutaro

AU - Omori, Akina

AU - Matsumoto, Megumi

AU - Watanabe, Yuki

AU - Hoshina, Kyoko

AU - Tanaka, Marenao

AU - Moniwa, Norihito

AU - Yoshida, Hideaki

AU - Ishii, Junichi

AU - Miura, Tetsuji

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Fatty acid binding protein 4 (FABP4), also known as adipocyte FABP or aP2, is secreted from adipocytes in association with lipolysis as a novel adipokine, and elevated serum FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the modulation of serum FABP4 level by therapeutic drugs. Sitagliptin (50 mg/day), a dipeptidyl peptidase 4 (DPP-4) inhibitor that increases glucagon-like peptide 1 (GLP-1), was administered to patients with type 2 diabetes (n = 24) for 12 weeks. Treatment with sitagliptin decreased serum FABP4 concentration by 19.7% (17.8 ± 1.8 vs. 14.3 ± 1.5 ng/ml, P<0.001) and hemoglobin A1c without significant changes in adiposity or lipid variables. In 3T3-L1 adipocytes, sitagliptin or exendin-4, a GLP-1 receptor agonist, had no effect on short-term (2 h) secretion of FABP4. However, gene expression and long-term (24 h) secretion of FABP4 were significantly reduced by sitagliptin, which was not mimicked by exendin-4. Treatment with recombinant DPP-4 increased gene expression and long-term secretion of FABP4, and the effects were cancelled by sitagliptin. Furthermore, knockdown of DPP-4 in 3T3-L1 adipocytes decreased gene expression and long-term secretion of FABP4. In conclusion, sitagliptin decreases serum FABP4 level, at least in part, via reduction in the expression and consecutive secretion of FABP4 in adipocytes by direct inhibition of DPP-4.

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