New tool for treatment of obesity and type 2 diabetes: lipidized prolactin-releasing peptide analogs
| Main Author: | Andrea Popelov? |
|---|---|
| Format: | Proceeding poster |
| Terbitan: |
, 2016
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| Subjects: | |
| Online Access: |
https://zenodo.org/record/154327 |
Daftar Isi:
- Obesity is a frequent metabolic disorder with a steadily increasing prevalence worldwide. As obesity triggers other life-threatening diseases, including type 2 diabetes mellitus, hypertension, dyslipidemia and atherosclerosis, an effective therapy is needed. Anorexigenic neuropeptides have the potential to decrease food intake and ameliorate obesity and accompanying metabolic disturbances but are ineffective after peripheral application. We have designed several lipidized analogs of neuropeptide prolactin-releasing peptide (PrRP) which is involved in food intake regulation. Our PrRP analogs with palmitic acid attached through glutamic acid or short chain of polyethylene glycol at Lys11 showed binding affinity and signaling in cells with PrRP receptor similar to natural PrRP. Furthermore, peripheral administration of these analogs to free fed mice and rats induced strong and long-lasting anorexigenic effect and neuronal activation in the brain areas involved in food intake regulation. Moreover, these novel analogs revealed higher bioavailability compared to PrRP analogs palmitoylated at N-terminus without any linker, probably due to higher solubility and better absorption after subcutaneous administration in mice and rats. Finally, food intake and body weight decrease as well as improvement of glucose tolerance were observed in diet-induced mice and obese diabetic rats after chronic treatment with palmitoylated PrRP analogs. Our data suggest that lipidization of PrRP enhances its stability, as well as enables the peptide to cross blood-brain barrier after peripheral administration. Strong anorexigenic and body-weight-reducing effects make lipidized PrRP analogs attractive candidates for anti-obesity and anti-diabetic treatment.