Neurochemical phenotype of hypothalamic neurons showing Fos expression 23 h after intracranial AgRP.
Agouti-related protein (AgRP) is coexpressed with neuropeptide Y (NPY) in a population of neurons in the arcuate nucleus (ARC) of the hypothalamus and stimulates food intake for up to 7 days if injected intracerebroventricularly. The prolonged food intake stimulation does not seem to depend on continued competition at the melanocortin-4 receptor (MC4R), because the relatively specific MC4R agonist MTII regains its ability to suppress food intake 24 h after AgRP injection. Intracerebroventricular AgRP also stimulates c-Fos expression 24 h after injection in several brain areas, so the neurons exhibiting delayed Fos expression might be particularly important in feeding behavior. Thus we aimed to identify the neurochemical phenotype of some of these neurons in select hypothalamic areas, using double-label immunohistochemistry. AgRP-injected rats ingested significantly more chow (10.2 +/- 0.6 g) vs. saline controls (3.4 +/- 0.7 g) in the first 9 h (light phase) after injection. In the lateral hypothalamus (particularly the perifornical area) 23 h after injection, AgRP induced significantly more Fos vs. saline in orexin-A (OXA) neurons (25.6 +/- 4.9 vs. 4.8 +/- 3.1%), but not in melanin-concentrating hormone (MCH) or cocaine- and amphetamine-regulated transcript (CART) neurons. In the ARC, AgRP induced significantly more Fos in CART (40.6 +/- 5.9 vs. 13.4 +/- 1.8%) but not NPY neurons. In the paraventricular nucleus, there was no significant difference in Fos expression induced by AgRP vs. saline in oxytocin and CART neurons. We conclude that the long-lasting hyperphagia induced by AgRP is correlated with and possibly partially mediated by hyperactive OXA neurons in the lateral hypothalamus and CART neurons in the ARC, but not by NPY and MCH neurons. The substantial increase in light-phase food intake by AgRP supports a role for the arousing effects of OXA. Activation of CART neurons in the ARC (which likely coexpress proopiomelanocortin) could indicate attempts to activate counterregulatory decreases in food intake.
Zheng
Huiyuan
H
Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA.
Corkern
Michele M
MM
Crousillac
Scott M
SM
Patterson
Laurel M
LM
Phifer
Curtis B
CB
Berthoud
Hans-Rudolf
HR
D054369:Agouti-Related Protein; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002452:Cell Count; D004435:Eating / Q000187:drug effects / Q000502:physiology; D007028:Hypothalamic Hormones / Q000096:biosynthesis; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008543:Melanins / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000096:biosynthesis; D009479:Neuropeptides / Q000096:biosynthesis; D064446:Orexin Receptors; D000068797:Orexins; D010121:Oxytocin / Q000096:biosynthesis; D010641:Phenotype; D010907:Pituitary Hormones / Q000096:biosynthesis; D011506:Proteins / Q000008:administration & dosage*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D018000:Receptors, Peptide / Q000819:agonists; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D002352:Carrier Proteins; D007028:Hypothalamic Hormones; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D010907:Pituitary Hormones; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D044105:Receptor, Melanocortin, Type 4; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D018000:Receptors, Peptide; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D010121:Oxytocin; C019463:melanin-concentrating hormone