Research Article Pharmacological Effects of JTT-551, a Novel Protein Tyrosine Phosphatase 1B Inhibitor, in Diet-Induced Obesity Mice

Copyright © 2014 Makoto Ito et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin signaling as well as insulin signaling. JTT-551 is a new PTP1B inhibitor, which is reported to improve glucose metabolism by enhancement of insulin signaling. We have evaluated an antiobesity effect of JTT-551 using diet-induced obesity (DIO) mice. A single administration of JTT-551 was provided to DIOmice with or without leptin, and DIO mice were given food containing JTT-551 for six weeks. A single administration of JTT-551 with leptin treatment enhanced the food inhibition and the signal transducer and activator of transcription 3 (STAT3) phosphorylation in hypothalamus. Moreover, chronic administration of JTT-551 showed an antiobesity effect and an improvement of glucose and lipid metabolism in DIOmice. JTT-551 shows an antiobesity effect possibly by enhancement of leptin signaling and could be useful in the treatment of type 2 diabetes and obesity. 1