title: Peptide YY levels are decreased by fasting and elevated following caloric intake but are not regulated by leptin.
abstract: OBJECTIVE
  Peptide YY (PYY) is a gut-derived 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.
  
  
  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 short-term 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
  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.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Chan
authors.forename: V
authors.initials: V
authors.lastname: Stoyneva
authors.forename: T
authors.initials: T
authors.lastname: Kelesidis
authors.forename: P
authors.initials: P
authors.lastname: Raciti
authors.forename: C S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D004435:Eating / Q000502:physiology; D002149:Energy Intake; D005215:Fasting / Q000502:physiology*; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D019894:Peptide YY / Q000097:blood*; D011994:Recombinant Proteins / Q000494:pharmacology; D013851:Thinness
chemical_list: D020738:Leptin; D011994:Recombinant Proteins; D019894:Peptide YY