Attenuated peptide YY release in obese subjects is associated with reduced satiety.
The responses of the gut hormone peptide YY (PYY) to food were investigated in 20 normal-weight and 20 obese humans in response to six test meals of varying calorie content. Human volunteers had a graded rise in plasma PYY (R2 = 0.96; P < 0.001) during increasing calorific meals, but the obese subjects had a lower endogenous PYY response at each meal size (P < 0.05 at all levels). The ratio of plasma PYY(1-36) to PYY(3-36) was similar in normal-weight and obese subjects. The effect on food intake and satiety of graded doses of exogenous PYY(3-36) was also evaluated in 12 human volunteers. Stepwise increasing doses of exogenous PYY(3-36) in humans caused a graded reduction in food intake (R2 = 0.38; P < 0.001). In high-fat-fed (HF) mice that became obese and low-fat-fed mice that remained normal weight, we measured plasma PYY, tissue PYY, and PYY mRNA levels and assessed the effect of exogenous administered PYY(3-36) on food intake in HF mice. HF mice remained sensitive to the anorectic effects of exogenous ip PYY(3-36). Compared with low-fat-fed fed mice, the HF mice had lower endogenous plasma PYY and higher tissue PYY but similar PYY mRNA levels, suggesting a possible reduction of PYY release. Thus, fasting and postprandial endogenous plasma PYY levels were attenuated in obese humans and rodents. The PYY(3-36) infusion study showed that the degree of plasma PYY reduction in obese subjects were likely associated with decreased satiety and relatively increased food intake. We conclude that obese subjects have a PYY deficiency that would reduce satiety and could thus reinforce their obesity.
le Roux
C W
CW
Department of Metabolic Medicine, 6th Floor Commonwealth Building, Hammersmith Hospital, Imperial College London, London W12 0NN, United Kingdom.
Batterham
R L
RL
Aylwin
S J B
SJ
Patterson
M
M
Borg
C M
CM
Wynne
K J
KJ
Kent
A
A
Vincent
R P
RP
Gardiner
J
J
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D001835:Body Weight; D004435:Eating / Q000502:physiology; D002149:Energy Intake; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009765:Obesity / Q000503:physiopathology*; D019894:Peptide YY / Q000378:metabolism*; D019518:Postprandial Period / Q000502:physiology*; D012016:Reference Values; D012528:Satiety Response / Q000502:physiology*
D019894:Peptide YY