Obesity and the Regulation of Body Mass:- Short-Term Eating Behavior Is Set by Ghrelin and PYY3–36
Ghrelin is a peptide hormone (28 amino acids) produced in cells lining the stomach. It was originally recognized as the stimulus for the release of growth hormone (ghre is the Proto-Indo-European root of “grow”), then subsequently shown to be a powerful appetite stimulant that works on a shorter time scale (between meals) than leptin and insulin. Ghrelin receptors are located in the pituitary gland (presumably mediating growth hormone release) and in the hypothalamus (affecting appetite), as well as in heart muscle and adipose tissue. The concentration of ghrelin in the blood varies strikingly between meals, peaking just before a meal and dropping sharply just after the meal (Fig. 1). Injection of ghrelin into humans produces immediate sensations of intense hunger. Individuals with Prader-Willi syndrome, whose blood levels of ghrelin are exception ally high, have an uncontrollable appetite, leading to extreme obesity that often results in death before the age of 30.
PYY3–36 is a peptide hormone (34 amino acids) secreted by endocrine cells in the lining of the small intestine and colon in response to food entering from the stomach. The level of PYY3–36 in the blood rises after a meal and remains high for some hours. It is carried in the blood to the arcuate nucleus, where it acts on orexigenic neurons, inhibiting NPY release and reducing hunger . Humans injected with PYY3–36 feel little hunger and eat less than normal amounts for about 12 hours.
This interlocking system of neuroendocrine controls of food intake and metabolism presumably evolved to protect against starvation and to eliminate counterproductive accumulation of fat (extreme obesity). The difficulty most people face in trying to lose weight testifies to the remarkable effectiveness of these controls.
FIGURE 1 Variations in ghrelin and insulin relative to meal times. (a) Plasma levels of ghrelin rise sharply just before the normal time for meals (7 a.m. breakfast, 12 noon lunch, 5:30 p.m. dinner) and drop precipitously just after meals, paralleling the subjective feelings of hunger. (b) Insulin levels rise immediately after each meal, in response to the increase in blood glucose concentration.
