EFFETTO DELLA VELOCITÀ DI ASSUNZIONE DI CIBO E DELLA PALATABILITA¿ SULLA SECREZIONE DI PEPTIDI GASTROINTESTINALI NELL¿ OBESITA¿ SEMPLICE E GENETICA.

Anorexigenic gastrointestinal hormones as peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and orexigenic hormone ghrelin influence the activity of the arcuate nucleus (ARC) neurons in the hypothalamous. The ARC plays a crucial role in the regulation of food intake and energy homeostasis. In contrast, the mesolimbic dopamine system encodes subjective ‘liking’ and ‘wanting’ of palatable foods, which is subjected to modulation by the hindbrain and the hypothalamic homeostatic circuits and by satiety and adiposity hormones. Reportedly, obesity reflects an energy imbalance in which genetically susceptible individuals become increasingly vulnerable to an ‘obesogenic’ environment. Dietary and behavioral approaches to severe obesity are frequently associated with limited persistent success over the time rendering bariatric surgery one of the more promising therapy for “super-obese” patients. Laparoscopic sleeve gastrectomy (LSG) is a purely “restrictive” operation applied in patients with body mass index (BMI) <50 kg/m2. Although early enthusiastic results on weight loss after LSG have been published, the underlying mechanism(s) of weight loss is still unknown and it could involve pos-LSG alterations of gastrointestinal hormones. Nowadays the number of overweight and obese people in the world are roughly 2 billion in 2013. The lifestyle of the modern civilization facilitates diffusion of fast feeding and, consequently, high energy intake. At the same time hedonic hunger may powerfully stimulate food intake in an environment where highly palatable foods are omnipresent and contribute to the diffusion of overweight and obesity. Therefore, understanding the physiological mechanisms underlying these eating behaviors may help to contrast it. The anorexigenic action of PYY is preserved in obese patients, although the circulating level of the peptide is low during fast and postprandial phase. obese individuals actually display low circulating ghrelin levels that could suggest greater sensitivity to the hormone. A pathogenic role for ghrelin has been suggested in individuals with genomic obesity as Prader–Willi syndrome, where hyperghrelinism precedes the development of obesity. On the contrary, only few studies have investigated postprandial GLP-1 and PYY in PWS, besides reporting conflicting results. Since the critical rule of gastrointestinal hormones in homeostatic and hedonic regulation of food intake and in the physiophatology of obesity we decided to study dynamically their secretion in association with eating behavior involved with the development of obesity. Particularly we conducted three studies: Study 1: evaluation of post-prandial anorexigenic gut peptide, appetite and glucometabolic responses at different eating rates in obese patients undergoing laparoscopic sleeve gastrectomy. Aim of this study was to determine whether eating the same meal at different rates (fast vs. slow feeding) evokes different post-prandial anorexigenic gut peptide responses in ten obese patients undergoing LSG. Circulating levels of GLP-1, PYY, glucose, insulin and triglycerides were measured before and 3 months after LSG. Visual analog scales were used to evaluate the subjective feelings of hunger and satiety. Irrespective of the operative state, either fast or slow feeding did not stimulate GLP-1 release (vs. 0 min); plasma levels of PYY were increased (vs. 0 min) by fast and slow feeding only after LSG. There were no differences in post-prandial levels of GLP-1 when comparing fast to slow feeding or pre- to post-operative state. Plasma levels of PYY after fast or slow feeding were higher in post- than preoperative state, with no differences when comparing PYY release after fast and slow feeding. Hunger and satiety were decreased and increased, respectively, (vs. 0 min) by food intake. Fast feeding evoked a higher satiety than slow feeding in either preor post-operative state, with no differences in hunger. In pre- or post-operative state there were similar responses for hunger and satiety after food intake. Finally, LSG improved insulin resistance after either fast or slow feeding. These (negative) findings would suggest a negligible contribution of the anorexigenic gut peptide responses in LSG-induced weight loss. Study 2: anticipatory and consummatory effects of (hedonic) chocolate intake on PYY, GLP-1, ghrelin and endocannabinoid secretion in obese adults previously satiated. To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), anandamide (AEA), 2-AG, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) in 10 satiated severely obese subjects after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same bromatologic composition. Evaluation of hunger and satiety was also performed by visual analogic scale. The anticipatory phase and the consumption of food for pleasure were associated with increased circulating levels of ghrelin, AEA, 2-AG, and OEA. In contrast, the levels of GLP-1, PYY, and PEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were higher and lower, respectively, in the hedonic session than in the non-palatable one. When motivation to eat is generated by exposure to, and consumption of, chocolate a peripheral activation of specific endogenous rewarding chemical signals, including ghrelin, AEA, and 2-AG, is observed in obese subjects. Although preliminary, these findings predict the effectiveness of ghrelin and endocannabinoid antagonists in the treatment of obesity. Study 3: evaluation of post-prandial anorexigenic gut peptide, appetite and glucometaboplic responses at different eatin rates in adult PWS patients The effect of eating rate on the release of anorexigenic gut peptides in Prader-Willi syndrome (PWS), a neurogenetic disorder clinically characterized by hyperphagia and excessive obesity, has not been investigated so far.Postprandial PYY and GLP-1 levels to fast (5 min) and slow (30 min) ice cream consumption were measured in PWS adult patients and age-matched patients with simple obesity and normal-weighted subjects. Visual analog scales (VASs) were used to evaluate the subjective feelings of hunger and satiety. Fast ice cream consumption stimulated GLP-1 release in normal subjects, a greater increase being observed with slow feeding. Fast or slow feeding did not change circulating levels of GLP-1 in obese patients, while, unexpectedly, fast feeding (but not slow feeding) stimulated GLP-1 release in PWS patients. Plasma PYY concentrations increased in all groups, irrespective of the eating rate. Slow feeding was more effective in stimulating PYY release in normal subjects, while fast feeding was more effective in PWS patients. Slow feeding evoked a lower hunger and higher satiety compared with fast feeding in normal subjects, this finding being not evident in obese patients. Unexpectedly, fast feeding evoked a lower hunger and higher satiety in PWS patients in comparison with slow feeding. Fast feeding leads to higher concentrations of anorexigenic gut peptides and favours satiety in PWS adult patients, this pattern being not evident in age-matched patients with simple obesity, thus suggesting the existence of a different pathophysiological substrate in these two clinical conditions.