Peptide YY
PYY is a 36-amino-acid peptide secreted by L cells in the ileum and colon in response to feeding. Intravenous infusion of PYY reduces appetite in humans. PYY belongs to the PP-fold family and shares structural homology with neuropeptide Y and pancreatic polypeptide. PYY1-36 and PYY3-36 are two forms of PYY, whereas the major circulating form is a truncated 34-amino-acid form, PYY3-36, created by cleavage of the N-terminal Tyr-Pro residues by dipeptidyl peptidase-4. PYY3-36 shows selectivity for the Y2 receptor with high affinity, although it has some affinity for Y1 and Y5 receptors. The Y2 receptor is thought to function as an auto-inhibitory presynaptic receptor, expressed on NPY neurons. In addition to its anorectic action when administered alone, PYY3-36 acts synergistically with GLP-1 receptor agonist, such as GLP-1 and oxyntomodulin, to reduce food intake in mice and humans.
PYY has been reported to exhibit an anti-inflammatory property. An in vitro study demonstrated that PYY attenuates transcription factor activities, including NF-κB, Smad3/4 and peroxisome proliferator-activated receptors [α/γα/γ (PRAR-α/γ)], in acinar cells of a TNF-α-induced rodent pancreatitis. Intravenous infusion of PYY delayed gastric emptying in healthy adults, while plasma PYY concentrations correlated with impaired gastric emptying in critically ill patients. In addition, plasma PYY concentrations were shown to be positively correlated with postprandial energy expenditure. Due to its pleiotropic effects on modulating appetite, inflammation, gastric motility and energy expenditure, PYY might be a candidate for regulating energy balance during inflammation in patients with RA. The results from our published report indicate that long-term therapy with etanercept cannot affect fasting plasma PYY levels, despite weight gain. No change in plasma PYY after the oral glucose challenge was observed before and after anti-TNF treatment in these patients. Hence plasma PYY may contribute minimally to the regulation of energy balance in patients with RA during anti-TNF therapy.