کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5514609 | 1541685 | 2017 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: PEGylated neuromedin U-8 shows long-lasting anorectic activity and anti-obesity effect in mice by peripheral administration PEGylated neuromedin U-8 shows long-lasting anorectic activity and anti-obesity effect in mice by peripheral administration](/preview/png/5514609.png)
- Intraperitoneal injection of neuromedin U-23 and neuromedin S inhibited food intake.
- PEGylation gave neuromedin U-8 a long-lasting anorectic activity.
- Subcutaneous injection of PEGylated neuromedin U-8 exerted an anti-obesity effect.
Neuromedin U (NMU) is a neuropeptide found in the brain and gastrointestinal tract. The NMU system has been shown to regulate energy homeostasis by both a central and a peripheral mechanism. Peripheral administration of human NMU-25 was recently shown to inhibit food intake in mice. We examined the possibility that other NMU-related peptides exert an anorectic activity by intraperitoneal (i.p.) administration. We found that rat NMU-23 and its structurally-related peptide rat neuromedin S (NMS) significantly reduced food intake in lean mice, whereas NMU-8, an active fragment of the octapeptide sequence conserved in porcine, human and mouse NMU, had no effect. When rat NMU-23, NMU-8, and rat NMS were covalently conjugated to polyethylene glycol (PEG) (PEGylation) at the N-terminus of these peptides, PEGylated NMU-8 showed the most long-lasting and robust anorectic activity. The exploration of the linker between NMU-8 and PEG using hetero-bifunctional chemical cross-linkers led to an identification of PEGylated NMU-8 analogs with higher affinity for NMU receptors and with more potent anorectic activity in lean mice. The PEGylated NMU-8 showed potent and robust anorectic activity and anti-obesity effect in diet-induced obesity (DIO) mice by once-daily subcutaneous (s.c.) administration. These results suggest that PEGylated NMU-8 has the therapeutic potential for treatment of obesity.
114
Journal: Peptides - Volume 94, August 2017, Pages 99-105