Journal of Lipid Research
Volume 56, Issue 12, December 2015, Pages 2372-2380
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Patient-Oriented and Epidemiological Research
Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus

https://doi.org/10.1194/jlr.M059469Get rights and content
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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.

fatty acid binding protein 4
adipokine
adipocyte
glucagon-like peptide 1

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M.F. has been supported by grants from the Japan Society for the Promotion of Science, Ministry of Education, Culture, Sports, Science and Technology (MEXT) Translational Research Network Program, Uehara Memorial Foundation, Senshin Medical Research Foundation, Japan Diabetes Foundation, Takeda Medical Research Foundation, Ono Medical Research Foundation, Takeda Science Foundation, Akiyama Life Science Foundation, Yamaguchi Endocrine Research Foundation, Naito Foundation Natural Science Scholarship, Suhara Memorial Foundation, and Kondou Kinen Medical Foundation. The authors declare no conflict of interest.

The online version of this article (available at http://www.jlr.org) contains a supplement.

    Abbreviations:

    1

    5-AG, 1,5-anhydroglucitol

    C/EBPα

    CCAAT/enhancer binding protein α

    CL

    cell lysate

    CM

    conditioned medium

    Cr

    creatinine

    DPP-4

    dipeptidyl peptidase 4

    eGFR

    estimated glomerular filtration rate

    FABP

    fatty acid binding protein

    FABP4

    fatty acid binding protein 4

    GIP

    gastric inhibitory polypeptide

    GLP-1

    glucagon-like peptide 1

    M/F

    male/female