Intestinal feedback signaling and satiety.

Peptidergic and neural signals arising from the presence of food in the gastrointestinal track provide feedback signals to the brain about the nature and quantity of consumed nutrients. Peptide secreting cells are differentially distributed along the gastrointestinal tract. How ingested nutrients activate or inhibit peptide secretion is complex and depends upon local, hormonal and neural mechanisms. The mode of action of the various peptides is equally complex involving endocrine, paracrine and neurocrine signaling. The success of bariatric surgical approaches to obesity treatment is secondary to alterations in gastrointestinal feedback signaling and roles of increased secretion of lower gut peptides such as peptide YY (PYY) and glucagon like peptide 1 (GLP-1) in mediating the superior effects of Roux-en-Y gastric bypass (RYGB) surgery are becoming evident. Direct nutrient delivery to jejunal sites that models the site of gastric-jejunal anastamosis in RYGB is especially effective at inhibiting food intake. Such infusions also stimulate the release of lower gut peptides suggesting a role for increased gut peptide signaling in sustaining such feeding inhibitions. Thus, gut peptides are clear targets for future obesity therapeutic developments.