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I.R.F. / Aging news / General / 02121301

Gut hormone PYY3-36, food intake and longevity
Posted on: December 13, 2002

It is well known that calorie restriction prolongs life span in rodents. This works by slowing metabolic rate, and lowering the amount of free radicals, as they are generated mostly by mitochondria, during oxidative phosphorilation process. Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY3-36 (PYY3-36), an Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Scientists have shown* that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway*. Compounds working on inhibition of appetite, leading to reduced food intake may help not only to reduce weight, but make people live longer and stay healthier. But this statement could not be posted as true as we don't know the influence of calorie restriction to Homo sapiens.

Source: *Rachel I. Batterham, Michael A. Cowley, Caroline J. Small, Herbert Herzog, Mark A. Cohen, Catherine I. Dakin, Alison M. Wren, Audrey E. Brynes, Malcolm J. Low, Mohammad A. Ghatei, Roger D. Cone & Stephen R. Bloom; Gut hormone PYY3-36 physiologically inhibits food intake; Nature 418, 650 - 654 (2002)
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