STUDY OF DIETARY FACTORS FOR BODY WEIGHT CONTROL THROUGH GUT BRAIN-AXIS

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

Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut-liver axis

Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P\ua0<\ua00\ub701) and serum cholesterol (P\ua0<\ua00\ub7001), alanine aminotransferase and glucose (P\ua0<\ua00\ub705). Accordingly, liver PPAR- \u3b1 (P\ua0<\ua00\ub705) and acyl-CoA oxidase-1 (P\ua0<\ua00\ub705) as well as duodenal ATP-binding cassette (ABC) subfamily A1 (ABCA1) and subfamily G1 (ABCG1) (P\ua0<\ua00\ub705) mRNA expressions increased with coffee consumption. Compared with HFD animals, HFD+COFFEE mice had more undigested lipids in the caecal content and higher free fatty acid receptor-1 mRNA expression in the duodenum and colon. Furthermore, they showed an up-regulation of duodenal and colonic zonulin-1 (P\ua0<\ua00\ub705), duodenal claudin (P\ua0<\ua00\ub705) and duodenal peptide YY (P\ua0<\ua00\ub705) mRNA as well as a higher abundance of Alcaligenaceae in the faeces (P\ua0<\ua00\ub705). HFD+COFFEE mice had an energy intake comparable with HFD-fed mice but starting from the eighth intervention week they gained significantly less weight over time. Data altogether showed that coffee supplementation prevented HFD-induced NAFLD in mice by reducing hepatic fat deposition and metabolic derangement through modification of pathways underpinning liver fat oxidation, intestinal cholesterol efflux, energy metabolism and gut permeability. The hepatic and metabolic benefits induced by coffee were accompanied by changes in the gut microbiota

Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake

ObjectivesThis study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.DesignEighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.ResultsIncreased MD adherence in the MedD group successfully reprogrammed subjects' intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.ConclusionSwitching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health

Ethanolamine Produced from Oleoylethanolamide Degradation Contributes to Acetylcholine/Dopamine Balance Modulating Eating Behavior

International audienceOleoylethanolamide is a well-recognized anorectic compound which also has noteworthy effects on food-reward, influencing the acetylcholine (ACh)/dopamine (DA) balance in the cholinergic system. After its administration, oleoylethanolamide is quickly degraded into oleic acid and ethanolamine. The effect of oleic acid on the gut-brain axis has been extensively investigated, whereas ethanolamine has received scarce attention. However, there is scattered evidence from old and recent research that has underlined the influence of ethanolamine on the cholinergic system. In the present article, we propose a model by which the released ethanolamine contributes to the overall balance between DA and ACh after oleoylethanolamide administration

Oleic acid content of a meal promotes oleoylethanolamide response and reduces subsequent energy intake in humans

Animal data suggest that dietary fat composition may influence endocannabinoid (EC) response and dietary behavior. This study tested the hypothesis that fatty acid composition of a meal can influence the short-term response of ECs and subsequent energy intake in humans. Fifteen volunteers on three occasions were randomly offered a meal containing 30 g of bread and 30 mL of one of three selected oils: sunflower oil (SO), high oleic sunflower oil (HOSO) and virgin olive oil (VOO). Plasma EC concentrations and appetite ratings over 2 h and energy intake over 24 h following the experimental meal were measured. Results showed that after HOSO and VOO consumption the circulating oleoylethanolamide (OEA) was significantly higher than after SO consumption; a concomitantly significant reduction of energy intake was found. For the first time the oleic acid content of a meal was demonstrated to increase the post-prandial response of circulating OEA and to reduce energy intake at subsequent meals in humans

Microencapsulated bitter compounds (from Gentiana lutea) reduce daily energy intakes in humans

Mounting evidence showed that bitter-tasting compounds modulate eating behaviour through bitter taste receptors in the gastrointestinal tract. This study aimed at evaluating the influence of microencapsulated bitter compounds on human appetite and energy intakes. A microencapsulated bitter ingredient (EBI) with a core of bitter Gentiana lutea root extract and a coating of ethylcellulose–stearate was developed and included in a vanilla microencapsulated bitter ingredient-enriched pudding (EBIP). The coating masked bitterness in the mouth, allowing the release of bitter secoiridoids in the gastrointestinal tract. A cross-over randomised study was performed: twenty healthy subjects consumed at breakfast EBIP (providing 100mg of secoiridoids) or the control pudding (CP) on two different occasions. Blood samples, glycaemia and appetite ratings were collected at baseline and 30, 60, 120 and 180min after breakfast. Gastrointestinal peptides, endocannabinoids (EC) and N-acylethanolamines (NAE) were measured in plasma samples. Energy intakes were measured at an ad libitum lunch 3 h after breakfast and over the rest of the day (post lunch) through food diaries. No significant difference in postprandial plasma responses of gastrointestinal hormones, glucose, EC and NAE and of appetite between EBIP and CP was found. However, a trend for a higher response of glucagon-like peptide-1 after EBIP than after CP was observed. EBIP determined a significant 30% lower energy intake over the post-lunch period compared with CP. These findings were consistent with the tailored release of bitter-tasting compounds from EBIP along the gastrointestinal tract. This study demonstrated that microencapsulated bitter secoiridoids were effective in reducing daily energy intake in humans

Salivary endocannabinoids and: N -acylethanolamines upon mastication of a semisolid food: Implications in fat taste, appetite and food liking

This study aimed to evaluate whether salivary endocannabinoid (EC) and N-acylethanolamine (NAE) concentrations upon mastication of a semisolid food were involved in the sensory perception of fat taste, food liking and appetite in humans. A fat-enriched (FEP) and a low-fat control (CP) pudding were developed and used in a randomized cross-over study with 19 healthy volunteers. The study protocol combined a Modified Sham-Feeding (MSF) with a multiple-spoon Temporal Dominance of Sensations method. Subjects masticated and expectorated 10 spoons of the pudding and selected the dominant sensations among a list of attributes. Saliva samples, appetite and food liking scores were collected at baseline, immediately after the MSF of the pudding and every 5 min until 20 min after MSF. Salivary concentrations of all monitored ECs and NAEs increased during pudding mastication compared to baseline (except for palmitoylethanolamide with FEP). The raise was lower with FEP than with CP for all compounds except for 2-arachidonoylglycerol whose increase was higher than the other compounds and independent of pudding type. Salivary N-arachidonoylethanolamine, linoleoylethanolamide and palmitoylethanolamide were significantly lower at 10 and 20 min after MSF of FEP than CP. Fatty taste at the 2nd spoon and creaminess at the 5th spoon were perceived as dominant with FEP whereas only wateriness was dominant with CP at the 2nd spoon. No difference between puddings for individual appetite or food liking over the 20 min of the protocol was recorded. During mastication of a semisolid fatenriched food, the fatty taste and the creaminess were perceived as dominant. Salivary ECs and NAEs were not associated with the individual perception of fatty taste, pudding liking and appetite sensations