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


METHODS
Rats 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.


RESULTS
Decreased 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.


CONCLUSIONS
These 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.
Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan. dykuo@csmu.edu.tw.
Yih-Shou
YS
Hsieh
Pei-Ni
PN
Chen
Ching-Han
CH
Yu
Jiuan-Miaw
JM
Liao
Dong-Yih
DY
Kuo
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001066:Appetite / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D047369:Chromatin Immunoprecipitation; D005247:Feeding Behavior / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D019805:alpha-Methyltyrosine / Q000008:administration & dosage / Q000494:pharmacology
C092926:BIBP 3226; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D044105:Receptor, Melanocortin, Type 4; D017476:Receptors, Neuropeptide Y; D018808:Transcription Factor AP-1; C097212:neuropeptide Y-Y1 receptor; D019805:alpha-Methyltyrosine; D001120:Arginine; D000661:Amphetamine