Obesity is an escalating epidemic, but an effective noninvasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated because peptides have a low stability and limited ability to cross the blood-brain barrier. In this review, we summarize results of several studies with our newly designed lipidized analogs of prolactin-releasing peptide (PrRP). PrRP is involved in feeding and energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF (NPFF)-2 receptor. Acute peripheral administration of myristoylated and palmitoylated PrRP analogs to mice and rats induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight, improved metabolic parameters and attenuated lipogenesis in mice with diet-induced obesity. A strong anorexigenic, body weight-reducing and glucose tolerance-improving effect of palmitoylated-PrRP31 was shown also in diet-induced obese rats after its repeated 2-week-long peripheral administration. Thus, the strong anorexigenic and body weight-reducing effects of palmitoylated PrRP31 and myristoylated PrRP20 make these analogs attractive candidates for antiobesity treatment. Moreover, PrRP receptor might be a new target for obesity therapy.

Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic Prague Czech Republic

Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic Prague Czech Republic Institute of PhysiologyAcademy of Sciences of the Czech Republic Prague Czech Republic

Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic Prague Czech Republic University of Chemistry and TechnologyPrague Czech Republic

References provided by Crossref.org

Lipidization as a tool toward peptide therapeutics

NPFFR2-deficient mice fed a high-fat diet develop strong intolerance to glucose

Metabolomic Study of Aging in fa/fa Rats: Multiplatform Urine and Serum Analysis

Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances

Lipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models

Cholecystokinin system is involved in the anorexigenic effect of peripherally applied palmitoylated prolactin-releasing peptide in fasted mice

Cellular Signaling and Anti-Apoptotic Effects of Prolactin-Releasing Peptide and Its Analog on SH-SY5Y Cells

Prolactin-Releasing Peptide: Physiological and Pharmacological Properties

Lipidized prolactin-releasing peptide improved glucose tolerance in metabolic syndrome: Koletsky and spontaneously hypertensive rat study

Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity