The neuropeptide Y Y1 receptor knockdown modulates activator protein 1-involved feeding behavior in amphetamine-treated rats

Abstract

BackgroundHypothalamic neuropeptide Y (NPY) and two immediate early genes, c-fos and c-jun, have been found to be involved in regulating the appetite-suppressing effect of amphetamine (AMPH). The present study investigated whether cerebral catecholamine (CA) might regulate NPY and POMC expression and whether NPY Y1 receptor (Y1R) participated in activator protein-1 (AP-1)–mediated feeding.MethodsRats were given AMPH daily for 4 days. Changes in the expression of NPY, Y1R, c-Fos, c-Jun, and AP-1 were assessed and compared.ResultsDecreased CA could modulate NPY and melanocortin receptor 4 (MC4R) expressions. NPY and food intake decreased the most on Day 2, but Y1R, c-Fos, and c-Jun increased by approximately 350%, 280%, and 300%, respectively, on Day 2. Similarly, AP-1/DNA binding activity was increased by about 180% on Day 2. The expression patterns in Y1R, c-Fos, c-Jun, and AP-1/DNA binding were opposite to those in NPY during AMPH treatment. Y1R knockdown was found to modulate the opposite regulation between NPY and AP-1, revealing an involvement of Y1R in regulating NPY/AP-1–mediated feeding.ConclusionsThese results point to a molecular mechanism of CA/NPY/Y1R/AP-1 signaling in the control of AMPH-mediated anorexia and may advance the medical research of anorectic and anti-obesity drugs.

Effects of drugs of abuse on the central neuropeptide Y system

“…Also, both Y 1 R knockdown or blockade could modulate the expression of NPY indicating the involvement of this receptor in the regulation of NPY‐mediated appetite suppression (Hsieh et al . ). The authors further suggest that Y 1 R might play an essential role that is consistent with the function of the proopiomelanocortin neurons (an anorexigenic transmission), but is opposite to that of NPY neurons (an orexigenic transmission).…”

“…In fact, Hsieh et al . () showed that anorectic response of AMPH was related to a decrease of NPY and to an opposite effect on Y 1 R expression, which was upregulated. Also, both Y 1 R knockdown or blockade could modulate the expression of NPY indicating the involvement of this receptor in the regulation of NPY‐mediated appetite suppression (Hsieh et al .…”

Neuropeptides Exert Neuroprotective Effects in Alzheimer's Disease

“…Neuropeptide Y is a 36-amino acid neuropeptide. Neuropeptide Y receptors are classified into five subtypes: Y1, Y2, Y4, Y5, and Y6 (Hsieh et al, 2013; Mittapalli and Roberts, 2014; Pérez-Fernández et al, 2014). Neuropeptide Y plays functions associated with modulation of food ingestion, mood, learning and memory (dos Santos et al, 2013b) and also plays an important role in neuroprotection against neurodegenerative diseases (Figure 4).…”

Impaired hypothalamic cocaine‐ and amphetamine‐regulated transcript expression in lateral hypothalamic area and paraventricular nuclei of dehydration‐induced anorexic rats

“…The NPY‐Y1 receptor has been linked to the regulation of CART neurones by amphetamine‐induced anorexia that increases peptide expression in rats . Another factor likely involved in unchanged CART mRNA levels in this subregion of the PVN in DIA rats is the overexpression of c‐jun and c‐fos (AP1) as in amphetamine‐induced anorexia because the CART promoter has an AP1‐binding site; thus, AP1 might be avoiding a reduction in CART levels as in FFR. This is worthy of study in the DIA model.…”