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The gut hormone fragment peptide YY 3-36 (PYY) is known to reduce appetite and food intake when given to
subjects of normal weight as well as to rodents. The authors investigated whether obese subjects were
also sensitive to the anorectic effects of PYY. They compared the effects of this peptide by infusing
it into 12 obese and 12 lean subjects in a double-blind, placebo-control, crossover study, and measured
the effects on appetite, food intake as well as plasma levels of PYY, ghrelin, leptin and insulin.
Caloric intake during a buffet lunch two hours after the infusion of PYY was significantly decreased by 30%
in the obese and by 31% in the lean subjects. PYY infusion also caused a significant decrease in the cumulative
24-hour calorie intake in both obese and lean subjects. The average decrease in the food ingestion was about
one-third of the calories, as compared to the amount consumed the day prior to the infusion. However, food
intake from 0-12 hours following PYY administration was more markedly reduced than that ingested from 12-24
hours after the infusion. The administration of PYY also reduced plasma levels of the appetite stimulatory
hormone, ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects
as compared to the non-obese group. Furthermore, the fasting PYY levels correlated negatively with BMI.
The authors concluded that obese subjects were not resistant to the anorectic effects of PYY and suggested
that a deficiency of PYY may contribute to the pathogenesis of obesity in humans.
Editor's Comment: PYY is secreted postprandially, in proportion to the calories
ingested, by endocrine L cells lining the distal small bowel and colon. PYY leads to a decrease food intake
by inhibiting gut motility and increasing satiety. In this study, PYY infusion reduced hunger in both the
obese and the lean individuals. These effects were directly related to the action of PYY, as there were no
effects on the palatability of meals, feelings of well being, or the presence of nausea. This peptide is one
of the many signals that have been recently identified providing short-term information to the hindbrain and
hypothalamus regarding hunger and satiety. Other gut hormones, such as cholecystokinin and ghrelin, also play
a role in communicating with the hypothalamus and brain stem to stimulate or reduce the appetite. In this
issue of GGH there is a review of ghrelin , the hunger hormone, acting on growth hormone secretagogue receptors
and its pathophysiologic role in obesity related diseases.1 However, the regulatory controls
of food intake are more complex and involve other endocrine functions of adipose tissue, principally leptin, and
appetite controlling genes as previously reviewed .2 However, PYY signal in satiety
appears to play a role in obesity in humans and could be thought of as a therapeutic agent; a hope that was not
shared by leptin, as in obesity there is marked resistance to the actions of this hormone. A graphic depicting
the complex interactions among hormonal and neural pathways that regulate food intake and body fat mass3
is shown below (Figure).
Fima Lifshitz , MD
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Interactions among Hormonal and Neural Pathways That Regulate Food Intake and Body-Fat Mass
In this schematic diagram of the brain, the dashed lines indicate hormonal inhibitory effects, and the solid lines
stimulatory effects. The paraventricular and arcuate nuclei each contain neurons that are capable of stimulating or
inhibiting food intake. Y1R and Y2R denote the Y1 and Y2 subtypes of the neuropeptide Y (NPY) receptor, MC4R melanocortin
4 receptor, PYY peptide YY 3–36 , GHsR growth hormone secretagogue receptor, AgRP agouti-related protein, POMC
proopiomelanocortin, a -MSH a -melanocyte–stimulating protein, LEPR leptin receptor, and INSR insulin receptor.
Reprinted with permission from Batterham RL, et al. Inhibition of food intake in obese subjects by peptide YY 3-36. N Engl J Med 2003;349:941-948.
Copyright © 2003 Massachusetts Medical Society. All Rights Reserved. |
References - (linked to  )
- Casanueva FF, Dieguez C. GGH 2004;20:1-8.
- Diamond F. GGH 2002; 18:17 -22.
- Korner J, Liebel R. N Eng J Med 2003;1349:926-928.
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Current GGH - Vol. 24 No. 1
Batterham RL, et al. Inhibition of food intake in obese subjects by peptide YY 3-36. N Engl J Med
2003;349:941-948.
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