Prolactin-releasing peptide: a new tool for obesity treatment

Abstract

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.

Prolactin-releasing peptide improved leptin hypothalamic signaling in obese mice

“…As shown in our recent studies, lipidization of PrRP31 not only increased its stability but also enabled PrRP31 to accomplish a central anorexigenic effect both in mice and rats with DIO , Holubova et al 2016, Kuneš et al 2016. In our previous studies, DIO in mice was shown to be associated with high levels of leptin (Matysková et al 2008) and leptin resistance (Matyskova et al 2010).…”

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

“…PrRP and its receptor may represent a new promising target for obesity treatment [ 28 ]. Our previous studies have demonstrated that the lipidization of PrRP enables its central anorexigenic effects after peripheral administration in both acute and chronic experiments [ 10 , 29 ].…”

Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health

“…185 Examples include gut include species of the genera Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, and Enterococcus. 186 There is increasing interest in exploring the beneficial features of next-generation probiotics or live therapeutic products which include species not traditionally considered as probiotics, such as Akkermansia muciniphila, 187 Faecalibacterium prausnitzii, 188 species of the genus Bacteroides, 189 and genetically modified Lactococcus strains carrying beneficial traits. 190 Recent evidence suggests that probiotic bacterial viability is not necessary to develop health-promoting effects in the host.…”