Peptide YY and Related Peptides

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Introduction

Peptide YY (PYY) is a peptide containing 36 amino acids. PYY has the same tertiary structure as the neuropeptide Y (NPY) and the pancreatic polypeptide (PP), including a α helix, a β fold, a proline helix to form a U shaped peptide, known as PP folding. The two major forms of PYY are PYY_1-36 and PYY_3-36, which have PP fold structural motifs. However, the most common form of circulating PYY immunoreactivity is PYY_3-36, which binds to the Y2 receptor (Y2R) of the Y family of receptors. PYY is a gut hormone that regulates appetite and inhibits pancreatic secretion. PYY and related peptides can mediate its effects through the neuropeptide Y receptors. PYY and related peptides exerts its action through NPY receptors. It inhibits gastric motility and increases water and electrolyte absorption in the colon. PYY and related peptides may also inhibit pancreatic secretion. Its role is to slow gastric emptying, thereby increasing the efficiency of after-meal digestion and nutrient absorption.

Mechanism of action

PYY and related peptides is an agonist at neuropeptide Y2 receptors (NPY2R), produced by L cells, which can reduce hunger and food intake in rodents, lean and obese people. The exact action sites of PYY and related peptides remain to be clarified. Electrophysiological, intra-arcuate administration and NPY2R antagonist studies suggest that PYY and related peptides acts directly in the hypothalamic circuits that regulate energy homeostasis, but additional work has implicated brainstem and vagal inputs. The secretion of PYY and related peptides depends on ganglionic transmission and an atropine-blocked parasympathetic pathway, the release of PYY and related peptides may be inhibited by the vagal cholinergic mechanism. The adrenergic pathway was not involved in the release of PYY from food stimulation, but the electrical stimulation of splanchnic nerve increased the basic level of PYY, suggesting that the sympathetic nervous system affected the release of PYY. So by regulating the release of PYY, it can provide a reasonable treatment for obesity.

Application of PYY and related peptides

Obesity is associated with many diseases including type 2 diabetes, obstructive sleep apnea, coronary heart disease, and some cancers. PYY and related peptides is a kind of intestinal hormone that deserves attention and opens up a new way for the treatment of obesity.

References

1. Zhang, T., Uchida, T., Gomez, G., Lluis, F., Thompson, J. C., & Greeley Jr, G. H. (1993). Neural regulation of peptide YY secretion. Regulatory peptides, 48(3), 321-328.
2. Batterham, R. L., Heffron, H., Kapoor, S., Chivers, J. E., Chandarana, K., Herzog, H., & Withers, D. J. (2006). Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell metabolism, 4(3), 223-233.
3. Acuna-Goycolea, C., Tamamaki, N., Yanagawa, Y., Obata, K., & van den Pol, A. N. (2005). Mechanisms of neuropeptide Y, peptide YY, and pancreatic polypeptide inhibition of identified green fluorescent protein-expressing GABA neurons in the hypothalamic neuroendocrine arcuate nucleus. Journal of Neuroscience, 25(32), 7406-7419.