Agouti Related Peptides

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Introduction

The agouti-related peptide (AgRP) is produced by AgRP/NPY neurons in the brain. AgRP and NPY are co-expressed to increase appetite and reduce metabolism and energy consumption. AgRP is a potent and long-lasting appetite stimulating substance encoded by the AgRP gene in human. AgRP is a paracrine signal molecule composed of 132 amino acids and is very stable to thermal denaturation and acid degradation. AgRP is mainly expressed in the hypothalamus and adrenal gland tissues, and is less expressed in the testis, kidney and lung.

Mechanism of action

It is reported that AgRP stimulates the hypothalamic-pituitary-adrenal axis to release adrenal cortex (ACTH), cortisol and prolactin. And AgRP also increases the response of adrenocortical hormone to IL-1β, suggesting that AgRP is involved in the regulation of neuroendocrine and the response to inflammation. AgRP is believed to be an inverse agonist of the melanocortin receptor, especially for MC3-R and MC4-R. The melanocortin receptors MC3-R and MC4-R are directly related to metabolism and body weight. These receptors are usually activated by melanocyte stimulating hormone (MSH) and inhibited by AgRP. MSH has an activation effect on most melanocortin receptors (except MC2-R), However, AgRP is only highly specific for MC3-R and MC4-R. This reverse agonism of AgRP not only has influence on MSH, but also reduces the produce of cAMP.

Application of Agouti Related Peptides

Accumulating evidence suggests that AgRP in the hypothalamus are essential for controlling energy balance. Therefore, AgRP is considered to be an important substance of energy balance so that scientists regard AgRP as a candidate gene for human obesity. There is also much evidence that AgRP has an inhibitory effect on the hypothalamic-pituitary-thyroid axis and inhibits hypothalamic thyroid stimulation of thyrotropin-releasing hormone expression to reduce thyroid hormone levels in the circulatory system. As AgRP plays an important role in energy metabolism, researchers spare much effort on the studies of AgRP for the treatment of some diseases like diabetes and obesity.

References

1. Gropp E, Shanabrough M, Borok E, et al. Agouti-related peptide expressing neurons are mandatory for feeding[J]. Nature Neuroscience, 2005, 8(10):1289-1291.
2. Mizuno T M, Makimura H, Silverstein J, et al. Fasting regulates hypothalamic neuropeptide Y, agouti-related peptide, and proopiomelanocortin in diabetic mice independent of changes in leptin or insulin[J]. Endocrinology, 1999, 140(10):4551-7.