Placental Neuropeptide Y (NPY) and NPY receptors expressions and serum NPY levels in preeclampsia

Neuropeptide Y (NPY) has been reported as a vasoconstrictive substance that might be associated with preeclampsia. NPY mediates different effects via its specific NPY receptors. NPY action via Y1 receptor (Y1R) and/or Y5 receptor (Y5R) induces vascular smooth muscle cells proliferation while it is implicated in angiogenesis via Y2 receptor (Y2R) and/or Y5R. The objectives of this study were to (1) compare placental NPY, Y1 receptor ( Y1R), Y2 receptor ( Y2R), and Y5 receptor ( Y5R) expressions between normal (NP) and preeclamptic (PE) pregnancies to determine whether gene expression of different NPY receptors are altered in the PE condition; (2) compare maternal serum NPY levels between NP and PE subjects; and (3) determine correlations between placental gene expressions as well as serum NPY levels with maternal and neonatal clinical parameters. There were 22 subjects each in the NP (gestational age 37–42 weeks) and PE (gestational age ≥34 weeks) groups. Clinical parameters and serum NPY levels were measured before delivery. NPY expression and serum NPY levels were comparable between NP and PE subjects. Y1R, Y2R, and Y5R expressions were significantly lower in PE than NP subjects. In all and NP subjects, placental Y2R showed the highest expression, tended to be higher than Y5R, and was significantly higher than Y1R. In PE subjects, placental Y2R was comparable to Y5R and both Y2R and Y5R were significantly higher than Y1R. The NPY receptor expression ratio between the PE/NP groups showed that it was lowest for Y2R (0.27) compared to Y1R (0.42) and Y5R (0.40) suggestive of decreased Y2R expression in PE subjects. In summary, a decrease in placental Y2R mRNA might be associated with abnormalities of placental angiogenesis which probably contributes to the pathophysiology of preeclampsia. The roles of NPY receptors mediating placental vascularization need to be further investigated. Impact statement Neuropeptide Y (NPY) has been reported as a vasoconstrictive substance which might be associated with preeclampsia. The novel findings of this study were that Y1R, Y2R, and Y5R expressions were significantly lower in the PE than the NP group. Moreover, the NPY receptor expression ratio between the PE/NP groups was lowest for Y2R (0.27) compared to Y1R (0.42) and Y5R (0.40) suggestive of a reduction of this receptor in the preeclampsia group. Our results suggested that decreased Y2R mRNA in the PE group might be associated with abnormalities of placental angiogenesis which probably contributes to the pathophysiology of preeclampsia.

Hypophagic effects of insulin are mediated via NPY1/NPY2 receptors in broiler cockerels

Neuropeptide Y (NPY) plays a mediatory role in cerebral insulin function by maintaining energy balance. The current study was designed to determine the role of insulin in food intake and its interaction with NPY receptors in 8 experiments using broiler cockerels (4 treatment groups per experiment, except for experiment 8). Chicks received control solution or 2.5, 5, or 10 ng of insulin in experiment 1 and control solution or 1.25, 2.5, or 5 μg of receptor antagonists B5063, SF22, or SML0891 in experiments 2, 3, and 4 through intracerebroventricular (ICV) injection, respectively. In experiments 5, 6, and 7, chicks received ICV injection of B5063, SF22, SML0891, or co-injection of an antagonist + insulin, control solution, and insulin. In experiment 8, blood glucose was measured. Insulin, B5063, and SML0891 decreased food intake, while SF22 led to an increase in food intake. The hypophagic effect of insulin was also reinforced by injection of B560, but ICV injection of SF22 destroyed this hypophagic effect of insulin and increased food intake (p < 0.05). However, SML0891 had no effect on decreased food intake induced by insulin (p > 0.05). At 30 min postinjection, blood sugar in the control group was higher than that in the insulin group (p < 0.05). Therefore, the NPY1 and NPY2 receptors mediate the hypophagic effect of insulin in broiler cockerels.

A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

Human neuropeptide Y (hNPY) is one of the most widely expressed neurotransmitters in the human central and peripheral nervous systems. It consists of 36 highly conserved amino acid residues, and was first isolated from the porcine hypothalamus in 1982. While it is the most recently discovered member of the pancreatic polypeptide family (which includes neuropeptide Y, gut-derived hormone peptide YY, and pancreatic polypeptide), NPY is the most abundant peptide found in the mammalian brain. In order to exert particular functions, NPY needs to bind to the NPY receptor to activate specific signaling pathways. NPY receptors belong to the class A or rhodopsin-like G-protein coupled receptor (GPCR) family and signal via cell-surface receptors. By binding to GPCRs, NPY plays a crucial role in various biological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. Abnormal regulation of NPY is involved in the development of a wide range of diseases, including obesity, hypertension, atherosclerosis, epilepsy, metabolic disorders, and many cancers. Thus far, five receptors have been cloned from mammals (Y1, Y2, Y4, Y5, and y6), but only four of these (hY1, hY2, hY4, and hY5) are functional in humans. In this review, we summarize the structural characteristics of human NPY receptors and their role in metabolic diseases.