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- W4295280479 abstract "Obesity is an escalating epidemic, but an effective non-invasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated by their peptide character. In order to overcome this unfavorable fact, we have applied the lipidization of neuropeptide prolactin-releasing peptide (PrRP), whose strong anorexigenic effect was demonstrated. A palmitoylated analog of human PrRP (h palm-PrRP31) was injected in free-fed Wistar rats by three routes: subcutaneous (s.c.), intraperitoneal (i.p) (both 5 mg/kg) and intravenous (i.v.) (from 0.01 to 0.5 mg/kg). We found a circulating compound in the blood after all three applications with the highest concentration after i.v. administration. This corresponds to the effect on food intake, which was also strongest after i.v. injection. Moreover, this is in agreement with the fact that the expression of c-Fos in specific brain regions involved in food intake regulation was also highest after intravenous application. Pharmacokinetic data are further supported by results obtained from dynamic light scattering and CD spectroscopy. Human palm-PrRP31 analog showed a strong tendency to micellize, and formation of aggregates suggested lower availability after i.p. or s.c. application. We have demonstrated that palm-PrRP influenced food intake even in free fed rats. Not surprisingly, the maximal effect was achieved after the intravenous application even though two orders of magnitude lower dose was used compared to both two other applications. We believe that palm-PrRP could have a potential as an antiobesity drug when its s.c. application would be improved." @default.
- W4295280479 created "2022-09-12" @default.
- W4295280479 creator A5006154101 @default.
- W4295280479 date "2022-09-01" @default.
- W4295280479 modified "2023-09-27" @default.
- W4295280479 title "PL02-01 Reconstructed human 3D tissue models in toxicology: from initial idea to the regulatory acceptance" @default.
- W4295280479 cites W3115275155 @default.
- W4295280479 doi "https://doi.org/10.1016/j.toxlet.2022.07.042" @default.
- W4295280479 hasPublicationYear "2022" @default.
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