Several hormones and bioactive peptides are secreted from specialized cells within the gastrointestinal tract. The stomach and small intestines are the major sites for the secretion of these proteins. Several of these factors, following release to the blood stream, have been known for some time to exert effects within the central nervous system that affect our desire to eat and also the level of satiety experienced following the consumption of food. These gut appetite regulating proteins are of two types: those that inhibit the desire for food are called anorexigenic factors, while those that stimulate our desire for food are called orexigenic. The majority of gut proteins that exert effects on appetite and satiety are anorexigenic, whereas, there is but a single gut peptide (ghrelin) that acts in an orexigenic manner in the brain. The anorexigenic gut peptides include protein tyrosine tyrosine (PYY), pancreatic polypeptide (PP), cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and apolipoprotein A-IV (apoA-IV).

For more details on the role of gut peptides in the regulation of appetite and feeding behaviors visit the Gut-Brain Interrelationships page of my web site.

A recent paper just e-published in the journal Obesity demonstrates that administration of two of these anorexigenic gut hormones PYY and PP in combination results in reduced feeding behavior in an additive manner in laboratory mice paving the way for their potential use in the treatment of obesity in humans.

Both PYY (the biologically active circulating form of PYY is called PYY3-36 because it contains amino acids 3-36 of the primary translation product of the PYY gene) and PP have previously been shown to potently inhibit food intake both animals and humans. The results of this study demonstrate that addition of both of these gut peptides simultaneously results in an inhibition of feeding behavior that is additive. In other words the repression of appetite in lab animals was significantly higher in mice receiving both hormones compared to mice receiving either hormone alone. These effects were exerted via two distinct neuronal pathways in the hypothalamus. The hypothalamus is a region of the brain critically involved in the integration of metabolic demands of the body with the stimulation or repression of appetite and feeding behaviors.

The take home from this study is that there is great potential for the use of combination therapies such as co-administration of PYY and PP agonists in the treatment of obesity. The advantages of dual administration therapies is that the doses of either compound could be reduced to lessen any potential for untoward side-effects, while still maintaining potent regulation of appetite and weight gain.


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