Journal
JOURNAL OF LIPID RESEARCH
Volume 56, Issue 12, Pages 2372-2380Publisher
ELSEVIER
DOI: 10.1194/jlr.M059469
Keywords
fatty acid binding protein 4; adipokine; adipocyte; glucagon-like peptide 1
Categories
Funding
- 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
- Kondou Kinen Medical Foundation
- Grants-in-Aid for Scientific Research [26461384] Funding Source: KAKEN
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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.
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