Peptide YY levels are decreased by fasting and elevated following caloric intake but are not regulated by leptin

Abstract

Aims/hypothesis: Peptide YY (PYY) is a gutderived hormone that has been shown to reduce short-term food intake in animals and humans. It has been proposed that deficiency of PYY contributes to obesity in humans. However, the physiology of PYY regulation by factors such as caloric restriction, or by other molecules important in energy homeostasis, e.g. leptin, remains to be fully elucidated. Materials and methods: We evaluated the effect on PYY levels of: (1) caloric ingestion (a mixed meal) in five healthy normal-weight subjects; (2) fasting for 2 or 3 days in eight lean men and seven lean women respectively; and (3) recombinant human leptin administration at physiological replacement and pharmacological doses. Results: PYY levels increased 50% after a mixed meal (p=0.01), and shortterm complete fasting for 2 or 3 days decreased leptin and PYY levels to 20-30% and 40-60% of baseline, respectively (both p<0.05). However, recombinant human leptin administration at physiological doses to restore the fasting-induced decrease of leptin levels and at pharmacological doses over the short term had no effect on PYY levels. Conclusions/interpretation: PYY increases after meal ingestion and decreases after fasting in a manner consistent with a meal-related signal of energy homeostasis. Importantly, circulating levels of this gut-secreted molecule are independent of regulation by leptin over the short term. These findings contribute towards our understanding of the homeostatic systems that regulate appetite in humans, including the possible redundancy of gastrointestinally secreted and adipocyte-secreted signals. This may be of importance for the future development of medications to treat obesity.

Leptin Does Not Directly Regulate the Pancreatic Hormones Amylin and Pancreatic Polypeptide

“…Thus, any potential synergistic effect of amylin and leptin to mediate weight loss is not likely to be due to alterations of amylin levels by leptin but rather related to central mechanisms. These findings are consistent with our previous findings that leptin and gastrointestinalsecreted hormones (e.g., ghrelin [40] and peptide YY [41]) are independently regulated and support the existence of redundancy in the systems that regulate energy homeostasis.…”

Peptide YY (PYY)3–36 modulates thyrotropin secretion in rats

“…However, in fasted rats, it is likely that inhibition of NPY neurons via arcuate Y2 receptors is the predominant mechanism leading to the increase in serum TSH. In fasting conditions, there is a higher NPY inhibitory tonus on TRH neurons (Fekete et al 2001) and, in addition, fasting was associated with reduced PYY 3-36 serum levels, as reported by others (Tovar et al 2004, Chan et al 2005, which may render the tissues more sensitive to PYY 3-36 action. Other reports support the concept that fasting enhances PYY 3-36 effects, such as those concerning the peptide action on gonadotropin secretion (Pinilla et al 2006) and on food intake (Challisa et al 2003, Riediger et al 2004.…”

“…Fasting is associated with reduced serum concentrations of PYY 3-36 (Tovar et al 2004, Chan et al 2005, and peripherally injected PYY 3-36 partly reversed the fasting-induced c-Fos expression in arcuate nucleus neurons of mice (Riediger et al 2004), suggesting a role for the peptide in fasting adaptation.…”

Appetite-regulatory hormone responses on the day following a prolonged bout of moderate-intensity exercise

“…A more long term influence of PYY on energy 331 homeostasis has also been suggested by associations that have been found 332 between PYY, substrate oxidation and resting metabolic rate (25,48). 333 334 Short-term food restriction (11,31) and reductions in body weight (16) have each 335 been shown to lower fasting and/or postprandial circulating levels of PYY. This 336 response is likely to be part of an adaptive mechanism defending energy 337 homeostasis.…”