Effects of chronic central nervous system administration of agouti-related protein in pair-fed animals.
The melanocortin receptor (MC3-R and MC4-R) antagonist, agouti-related protein (AGRP), is a potent stimulant of food intake. We examined the effect of chronic intracerebroventricular (ICV) AGRP treatment on energy metabolism and pituitary function in ad libitum fed rats and rats administered AGRP and then pair-fed to a saline control group. Chronic ICV AGRP (83-132) administration (1 nmol/day for 7 days) significantly increased food intake and body weight in ad libitum fed animals compared with saline-treated controls (body weight on day 7: 272 +/- 6 [saline] vs. 319 +/- 8 g [AGRP ad libitum fed]; P < 0.001). A significant increase in the epididymal fat pad weight, interscapular brown adipose tissue (BAT) weight, and plasma leptin was also observed in the ad libitum fed group. In the AGRP pair-fed group, a significant increase in the epididymal fat pad weight, BAT weight, and plasma leptin was again observed, suggesting that AGRP caused metabolic changes independent of increased food intake. BAT uncoupling protein 1 (UCP-1) content was significantly decreased compared with saline controls in both the AGRP ad libitum fed (21 +/- 8% of saline control; P < 0.01) and AGRP pair-fed groups (24 +/- 7% of saline control; P < 0.01). Plasma thyroid-stimulating hormone (TSH) was significantly suppressed compared with saline controls in both the AGRP ad libitum fed and AGRP pair-fed groups (3.5 +/- 0.3 [saline] vs. 2.7 +/- 0.4 [AGRP ad libitum fed] vs. 2.1 +/- 0.2 ng/ml [AGRP pair-fed]; P < 0.01). This study demonstrates that independent of its orexigenic effects, chronic AGRP treatment decreased BAT UCP-1, suppressed plasma TSH, and increased fat mass and plasma leptin, suggesting that it may play a role in energy expenditure.
Department of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
C J
CJ
Small
M S
MS
Kim
S A
SA
Stanley
J R
JR
Mitchell
K
K
Murphy
D G
DG
Morgan
M A
MA
Ghatei
S R
SR
Bloom
D000273:Adipose Tissue / Q000033:anatomy & histology; D002001:Adipose Tissue, Brown / Q000378:metabolism; D054369:Agouti-Related Protein; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D006728:Hormones / Q000097:blood; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D020738:Leptin / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D009929:Organ Size / Q000187:drug effects; D010907:Pituitary Hormones / Q000097:blood; D011506:Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D000071256:Uncoupling Protein 1
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D002352:Carrier Proteins; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010907:Pituitary Hormones; D011506:Proteins; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1