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Effects of chronic central nervous system administration of agouti-related protein in pair-fed animals.
- Source :
-
Diabetes [Diabetes] 2001 Feb; Vol. 50 (2), pp. 248-54. - Publication Year :
- 2001
-
Abstract
- 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.
- Subjects :
- Adipose Tissue anatomy & histology
Adipose Tissue, Brown metabolism
Agouti-Related Protein
Animals
Body Weight drug effects
Carrier Proteins metabolism
Eating drug effects
Hormones blood
Injections, Intraventricular
Intercellular Signaling Peptides and Proteins
Ion Channels
Leptin blood
Male
Membrane Proteins metabolism
Mitochondrial Proteins
Organ Size drug effects
Pituitary Hormones blood
Proteins pharmacology
Rats
Rats, Wistar
Time Factors
Uncoupling Protein 1
Central Nervous System physiology
Proteins administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 0012-1797
- Volume :
- 50
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 11272133
- Full Text :
- https://doi.org/10.2337/diabetes.50.2.248