title: Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus.
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.
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan furuhasi@sapmed.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Furuhashi
authors.affiliation: Hiramitsu Heart Clinic, Shiroshita-cho 2-35, Minami-ku, Nagoya 457-0047, Aichi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hiramitsu
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mita
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fuseya
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Shutaro
authors.initials: S
authors.lastname: Ishimura
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Akina
authors.initials: A
authors.lastname: Omori
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hoshina
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Marenao
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Moniwa
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Junnichi
authors.initials: J
authors.lastname: Ishii
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C493410:FABP4 protein, human; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D000068900:Sitagliptin Phosphate
keywords: adipocyte; adipokine; fatty acid binding protein 4; glucagon-like peptide 1