Gut hormone PYY3-36 physiologically inhibits food intake

Abstract

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 YY(3-36) (PYY(3-36)), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY(3-36) in rats inhibits food intake and reduces weight gain. PYY(3-36) also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY(3-36) increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY(3-36) inhibits food intake. PYY(3-36) also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY(3-36) significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY(3-36) may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.

Interaction of NPY compounds with the rat glucocorticoid-induced receptor (GIR) reveals similarity to the NPY–Y2 receptor

“…High affinity binding of PYY , an anorectic peptide, with rGIR may have relevance in satiety signaling. Interestingly, rGIR is expressed in the arcuate and NTS, two areas which are known to mediate the anorectic effects of PYY3-36 [2,16]. High blood-brain barrier permeability been reported for PYY [18], which may facilitate its interaction with rGIR in a manner similar to Y 2 receptors.…”

“…Data from these studies has been published in abstract form [25]. (2,200 Ci/mmole) was purchased from Perkin Elmer Life Sciences, Boston, MA. ( 125 I)-Peptide YY ), 1600-1800 Ci/mole, was either purchased from Phoenix Laboratories (Belmont, CA), or synthesized by iodinating commercial PYY following the chloramine-T procedure [21].…”

Body weight is regulated by the brain: a link between feeding and emotion

“…of feeding. [146][147][148][151][152][153][154][155] NPY neurons in the Arc may contribute to ORX's effects on food intake, as ORX neurons innervate this NPY neuronal population and stimulate it. 156 Presently, we will focus on the Y1-R, as accumulating evidence suggests that this Y-receptor subtype contributes to NPY action not only on consummatory behavior but also on emotional responses.…”

To subjugate NPY is to improve the quality of life and live longer

“…synthesis in ARC perikarya, storage and release in the terminal field in the ARC-PVN axis) showed the episodic rise and fall in NPY release to be temporally correlated with initiation and termination of the appetitive drive (36,39,40). Knowledge of this tight temporal relationship between neurosecretion and behavior greatly assisted in delineating the precise roles of afferent hormonal signals from the periphery, such as leptin from white adipose tissue (WAT), ghrelin and peptide YY (PYY 3 -36) from gastrointestinal tract and insulin from pancreas β-cells, in the release of NPY antecedent to meal initiation (3,4,8,22,35,42,44,52,53,55,60,64,65). Photoperiodic cues and the time of food availability also interact in modulating the periodic antecedent NPY neurosecretion in the ARC-PVN axis (36,39,40,55,60,65).…”

“…Since the demonstration of the potent appetite stimulating effects of neuropeptide Y (NPY) and cohorts in 1984 (18), these signaling molecules have been at the forefront of the intense research directed toward deciphering the dialogue between peripheral signals and hypothalamic circuits that orchestrate ingestive behavior in mammals (8,30,36,39,40,64). In addition to a pivotal role in hypothalamic integration of energy homeostasis, the hypothalamic NPY network has since been shown to play a role in neuroendocrine control of reproduction and lactation, fluid balance, growth, stress, temperature, general body metabolism and bone health (1,12,15,31,41,45,46,48,62).…”