Mennella, Ilario (2016) STUDY OF DIETARY FACTORS FOR BODY WEIGHT CONTROL THROUGH GUT BRAIN-AXIS. [Tesi di dottorato]

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The physiological systems underlying the appetite control involve associations between peripheral physiology and metabolism (glucose homeostasis and adiposity), which in turn are linked to various brain processes. All hormonal messengers released from enteroendocrine cells in the gut mucosa can inform the brain either through the circulation or via primary afferent neurons or both. Gut hormones and adipokines interact each other in the control of body weight. In particular, visceral fat accumulation causes chronic low-grade inflammation, which contributes to the initiation and progression of metabolic disorders. Chronic low-grade inflammation, caused by the constant higher release of pro-inflammatory adipokines from adipose tissue, disrupt the gut hormones signalling at central and peripheral leves in the control of appetite and body weight. In this scenario the experiments described in the present thesis investigated mechanisms involved in both gut and brain regulation of food intake. In the experiments described in the chapthers 2 and 3 we tested in animals and in humans the hypothesis that dietary whole grains (WG) fibers are able to control body weight through a mechanism involving appetite control and the reduction of infiammatory status. In charter 4 we described a method to mimic the WG slow release of antioxidant compounds using encapsulation. Finally, in charter 5 we tested the hypothesis that the fat taste can influence the cephalic phase of the digestion. From the studies described in the present thesis, it can be concluded that: 1. The consumption of WG in substitution of refined cereals reduce subclinical inflammation and this effect is strengthen when WG are combined with prebiotic fibre. In fact, together the consumption of WG resistant starch is able to modulate two main components of the GBA, helping to restabilising an healthier physiological condition: cytokines and gut-microbiota. This effect is mediated by the slow release of bound phenolic compounds which are released from the fibre matrix during the gut microbiota fermentation. Therefore, the addition of a prebiotic fibre able to stimulate the growth and the activity of the gut microbiota increase the release of phenols from WG cereals. 2. Novel ingredients can be designed using encapsulation to obtain a slow release of antioxidant compounds and increase their bioavailability. In fact, a key lesson from the study of phenolic compounds from WG is that the kinetic of their absorption follows a slow but constant pattern: this guarantee a stable antioxidant protection in the bloodstream. In the present thesis, we used curcuminoids as a natural antioxidant -ingredient well-know for their healthy properties and low-grade bioavailability. The same approach can be used for many others antioxidant compounds. 3. Food consumption can modulate the endocannabinoids system which in turn influence eating behaviour. During the cephalic phase of the digestion, when food is chewed and even before swallowing, a variation of the ECs in saliva and plasma already appear. This evidence suggest a main role of cephalic phase in the digestive processes related to meal initiation and meal termination.

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