Emilio Canovai

Obesity Impairs Oligopeptide/Amino Acid-Induced Ghrelin Release and Smooth Muscle Contractions in the Human Proximal Stomach

SCOPE The satiation properties of proteins involve effects on gut peptide release and gastrointestinal motility which may be altered during obesity. This study compares the in vitro response and role of amino acid (AA) taste receptors (TASR) in the effect of AAs and a casein hydrolysate on ghrelin release and smooth muscle (SM) contractions in the proximal gut of lean and obese patients. METHODS AND RESULTS Basal ghrelin release, measured from mucosal segments, is maximal in the fundus and decreased distally. Obesity selectively impaires the stimulatory effect of a casein hydrolyaste on ghrelin release in the fundus but does not affect its inhibitory effect in the small intestine (SI). The SM contractions induced by a casein hydrolysate and AAs are stronger in strips from the SI than from the fundus but are reduced in the stomach of obese patients. The region-dependent expression of AA-TASRs in the mucosa and SM layer is affected by obesity. Most of the AA-induced responses are reduced by the umami antagonist, lactisole. l-Met-induced responses involve bitter taste receptors. CONCLUSION Region-specific targeting of AA taste receptors on both enteroendocrine and SM cells with specific AA-enriched diets might be a useful strategy to combat obesity as well as hypomotility disorders.

The expanding role of the bile acid receptor farnesoid X in the intestine and its potential clinical implications

Abstract Knowledge about the role of farnesoid X receptor (FXR) in the intestine is rapidly expanding. In pre-clinical animal models of inflammatory bowel disease and bile duct ligation, FXR activation has proven to directly target the three pillars of intestinal homeostasis: intestinal permeability, inflammation and bacterial translocation. The protective role of FXR-ligands on this homeostasis has implications for many intestinal pathologies like inflammatory bowel disease, ischemia reperfusion injury, the metabolic syndrome, colon cancer and even diarrhea. In this review, we summarize the mechanisms by which FXR-activation exerts these protective effects and we discuss its potential clinical applications.