Inhibition of Food Intake in Obese Subjects by Peptide YY3–36
Rachel L.
Batterham, M.B., B.S., Mark A. Cohen, M.B., Ch.B., Sandra M.
Ellis, B.Sc., Carel W. Le Roux, M.B., Ch.B., Dominic J. Withers,
M.B., B.S., Ph.D., Gary S. Frost, Ph.D., Mohammad A. Ghatei,
Ph.D., and Stephen R. Bloom, M.D., D.Sc.
Background:
The gut hormone fragment peptide YY3–36 (PYY) reduces
appetite and food intake when infused into subjects of
normal weight. In common with the adipocyte hormone leptin,
PYY reduces food intake by modulating appetite circuits in
the hypothalamus. However, in obesity there is a
marked resistance to the action of leptin, which
greatly limits its therapeutic effectiveness. We
investigated whether obese subjects were also resistant
to the anorectic effects of PYY.
Methods: We
compared the effects of PYY infusion on appetite and
food intake in 12 obese and 12 lean subjects in a double-blind,
placebo-controlled, crossover study. The plasma levels of
PYY, ghrelin, leptin, and insulin were also
determined.
Results:
Caloric intake during a buffet lunch offered two hours after
the infusion of PYY was decreased by 30 percent in the obese
subjects (P<0.001) and 31 percent in the lean subjects (P<0.001).
PYY infusion also caused a significant decrease in
the cumulative 24-hour caloric intake in both obese and lean
subjects. PYY infusion reduced plasma levels of the
appetite-stimulatory hormone ghrelin. Endogenous
fasting and postprandial levels of PYY were
significantly lower in obese subjects (the mean [±SE]
fasting PYY levels were 10.2±0.7 pmol per liter in
the obese group and 16.9±0.8 pmol per liter in the
lean group, P<0.001). Furthermore, the fasting PYY levels
correlated negatively with the body-mass index (r = –0.84,
P<0.001).
Conclusions:
We found that obese subjects were not resistant to
the anorectic effects of PYY. Endogenous PYY levels were low
in the obese subjects, suggesting that PYY deficiency may contribute
to the pathogenesis of obesity.
Source Information
From the
Department of Metabolic Medicine, Imperial College Faculty of
Medicine at Hammersmith Campus, Du Cane Rd., London W12 0NN,
United Kingdom.
The full text
of this study is available from the New
England Journal of Medicine.
