Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron.
AgRP is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus.
AgRP is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure.
AgRP is one of the most potent and long-lasting of appetite stimulators.
The agouti-related peptide is encoded by the AGRP gene.
AgRP is a paracrine signaling molecule made of 112 amino acids,
Agouti-related protein is expressed primarily in the adrenal gland, subthalamic nucleus, and hypothalamus, with lower levels of expression in the testis, kidneys, and lungs.
The appetite-stimulating effects of AgRP are inhibited by the hormone leptin and activated by the hormone ghrelin.
Adipocytes secrete leptin in response to food intake.
This hormone acts in the arcuate nucleus and inhibits the AgRP/NPY neuron from releasing orexigenic peptides.
Ghrelin has receptors on NPY/AgRP neurons that stimulate the secretion of NPY and AgRP to increase appetite.
AgRP is stored in intracellular secretory granules and is secreted via a regulated pathway.
The transcriptional and secretory action of AgRP is regulated by inflammatory signals.
Levels of AgRP are increased during periods of fasting.
It has been found that AgRP stimulates the hypothalamic-pituitary-adrenocortical axis to release ACTH, cortisol and prolactin.
It also enhances the ACTH response to IL-1-beta, suggesting it may play a role in the modulation of neuroendocrine response to inflammation.
Conversely, AgRP-secreting neurons inhibit the release of thyrotropin releasing hormones (TRH) from the paraventricular nucleus (PVN), which may contribute to conservation of energy in starvation.
This pathway is part of a feedback loop, since TRH-secreting neurons from PVN stimulate AgRP neurons.
AGRP has been demonstrated to be a competitive antagonist of melanocortin receptors.
The melanocortin receptors, MC3-R and MC4-R, are directly linked to metabolism and body weight control, and are activated by the peptide hormone α-MSH (melanocyte-stimulating hormone) and antagonized by the agouti-related protein.
AgRP induces obesity by chronic antagonism of the MC4-R..
AgRP plasma levels have been found to be elevated in obese human males.
AgRP mRNA levels have been found to be down regulated following an acute stressful event.
Systems involved in the regulation of stress response and of energy balance are highly integrated: Loss or gain of AgRP function may result in inadequate responses to environmental events, such as stress, and have potential to contribute to the development of eating disorders.
Polymorphisms in the AgRP gene have been linked with anorexia nervosa, as well as obesity.
AgRP neurons are rapidly inhibited upon food presentation and the onset of eating.
AgRP neurons signal with Neuropeptide Y in order to allow for sustained feeding behavior that outlasts the activation of the neurons.
AgRP neurons are sensitive to satiety and hunger hormonal signals. One is an appetite stimulant,
Ghrelin which makes AgRP neurons more excitable through interactions with specialized ghrelin receptors.
Leptin modulates AgRP activity through potassium channels, which alter the excitability of the neurons.
This is evidenced by different projections of AgRP neurons to various areas of the brain driving different food related behaviors.
Certain projections promote increased food consumption, but not increased food odor investigation.