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. 2015 Dec;56(12):2372–2380. doi: 10.1194/jlr.M059469

Fig. 4.

Fig. 4.

Possible mechanisms of reduced FABP4 concentration caused by sitagliptin. FABP4 is secreted from adipocytes in association with lipolysis and may act as an adipokine for the development of insulin resistance and atherosclerosis, leading to cardiovascular events (3, 9). Sitagliptin, a DPP-4 inhibitor, slows GLP-1 degradation, thereby increasing endogenous GLP-1 concentration. The GLP-1 receptor has been reported to be expressed in the stromal vascular fraction of adipose tissue but not in adipocytes (39). Furthermore, exendin-4, a GLP-1 receptor agonist, did not affect expression and secretion of FABP4, suggesting that reduction in serum FABP4 level by sitagliptin is independent of a canonical GLP-1 receptor signaling in adipocytes. DPP-4 is released from cell surface in adipocytes (34), and soluble DPP-4 (sDPP-4) has been suggested to act as an adipokine (35), though the receptor for sDPP-4 remains obscure. Direct inhibition of sDPP-4 as an adipokine by sitagliptin may contribute to a decrease in the expression of FABP4 in adipocytes, consequently leading to a reduction in serum FABP4 level. Another possible explanation for the reduction in serum FABP4 levels by sitagliptin is a decrease in lipolysis via suppression of sympathetic nerve activation and/or inflammatory cytokines as pleiotropic effects of DPP-4 inhibitors.