Disease relevance of Agrp

• In contrast, Agrp mRNA concentrations remained suppressed by 45% in the pair-fed group after 7 days of AGRP infusion despite equal body weight compared to saline controls [1].
• The obesity observed following CNS administration of Agrp is the result of decreased energy expenditure and increased food intake [2].

High impact information on Agrp

• Intracerebroventricular (ICV) administration of Agrp (83-132) decreased plasma thyroid stimulating hormone (TSH) in fed male rats [3].
• This study indicates that the hypothalamic nuclei expressing MC4R vary in their sensitivity to Agrp and alpha-MSH with regard to their effect on feeding [4].
• No changes in feeding were seen after the administration of Agrp into the Arc, LHA, or VMN, but NDP-MSH suppressed food intake in the Arc and LHA [4].
• Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling [5].
• The ratio of hypothalamic Pomc to Agrp mRNA was elevated two-fold in ad libitum and pair-fed AGRP-injected rats, which is consistent with increased stimulation of central melanocortin signalling pathways [1].

Biological context of Agrp

• Agrp (83-132) (1 nmol) administered ICV did not block the anorectic effects of CART (55-102) (1 h food intake, 0.2 nmol CART (55-102), 2.7+/-0.8 g vs. CART (55-102)+Agrp (83-132), 2.6+/-0.6 g, P=0.87; saline control 5.4+/-0.3 g, P<0.001 vs. both groups) [6].
• Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure [2].
• CONCLUSION: Chronic CNS administration of Agrp decreases oxygen consumption and decreases the capacity of BAT to expend energy [2].

Anatomical context of Agrp

• Agrp (10 to 100 pmol) was injected into the hypothalamic paraventricular nucleus of satiated (a.m. and p.m. injections) and food-deprived rats, or was co-administered with 117 pmol Neuropeptide Y (NPY) [7].
• Agrp (1 nmol) delivered to the lateral cerebral ventricle, a dose known to cause orexigenic effects, was shown to partially block acquisition of LiCl-induced CTA [8].
• alpha-Melanocyte-stimulating hormone (alpha-MSH) is an agonist, and agouti-related protein (Agrp) an endogenous antagonist at the melanocortin 3 and 4 receptors which are found in the central nervous system (CNS) [9].
• The present studies first demonstrate that long-lasting and delayed increases in food intake are also evident when Agrp is microinjected into the dorsomedial nucleus of the hypothalamus (DMH) [10].

Associations of Agrp with chemical compounds

• In the first (choice) paradigm, Agrp only increased intake of the sucrose-containing diet [10].
• An 8% decrease in VO(2) measurements was observed following ICV Agrp treatment on day 1 [2].

Other interactions of Agrp

• Neuropeptide Y (NPY) and agouti-related protein (Agrp) are orexigenic [11].
• Agouti-related protein (Agrp) is an endogenous melanocortin-4 receptor antagonist implicated in the regulation of food intake [7].
• Agrp (83-132) also did not block the anorectic effects of GLP-1 or CRF (1 h food intake, 0.3 nmol CRF, 0.7+/-0.3 g vs. CRF+Agrp (83-132), 0.7+/-0.3 g, P=0.91; 3 nmol GLP-1, 1.9+/-0.4 g vs. GLP-1+Agrp (83-132), 1.1+/-0. 5 g, P=0.23; saline control 5.0+/-0.6 g, P<0.001 vs. all four groups) [6].
• Inhibitory effects of Agrp on acquisition of CTA and aversion-associated activation of oxytocin neurons parallel what has previously been shown with opioid receptor agonists [8].
• OBJECTIVE: To investigate whether the Agouti-related protein (Agrp), the melanocortin receptor antagonist, alters oxygen consumption, as a measure of energy expenditure [2].

Analytical, diagnostic and therapeutic context of Agrp

• At 8 h postinjection, Agrp increased feeding in the PVN by 218 +/- 23% (P < 0.005), in the DMN by 268 +/- 42% (P < 0.005), and in the MPO by 236 +/- 31% (P < 0.01) compared with a saline control group for each nucleus [4].
• Following exposure to the two diets, rats were injected via cannula aimed at the DMH with 100 pmol Agrp at 10:00 h and allowed ad libitum access to either: (1) a choice of both diets or (2) one of the diets alone [10].

References