Taste receptors in the gut: a chemosensitive mechanism from fish to human

The ingestion of a meal evokes a series of digestive processes, which consist of the essential functions of the digestive system: food transport, secretory activity, absorption of nutrients and the expulsion of undigested residues do not absorbed. The gastrointestinal chemosensitivity is characterized by cellular elements of the endocrine gastrointestinal mucosa and nerve fibers, in particular of vagal nature. A wide range of mediators endocrine and/or paracrine can be released from various endocrine cells in response to nutrients in the diet. These hormones, in addition to their direct activity, act through specific receptors activating some of the most important functions in the control of energy intake and energy homeostasis in the body. For integration of this complex system of control of gastrointestinal chemosensitivity, recent evidence demonstrates the presence of taste receptors (TR) belonging to the family of G proteins coupled receptor expressed in the mucosa of the gastrointestinal tract of different mammals and human. This thesis is divided into several research projects that have been conceived in order to clarify the relationship between TR and nutrients. To define this relationship I have used various scientific approaches, which have gone on to evaluate changes in signal molecules of TR, in particular of the α-transducin in the fasting state and after refeeding with standard diet in the gastrointestinal tract of the pig, the mapping of the same molecule signal in the gastrointestinal tract of fish (Dicentrarchus labrax), the signaling pathway of bitter TR in the STC-1 endocrine cell line and finally the involvement of bitter TR in particular of T2R38 in patients with an excessive caloric intake. The results showed how there is a close correlation between nutrients, TR and hormonal release and how they are useful both in taste perception but also likely to be involved in chronic diseases such as obesity.L’ingestione di un pasto evoca una serie di processi digestivi che consistono nelle funzioni essenziali dell’apparato digerente, trasporto degli alimenti, attività secretiva, assorbimento dei nutrienti digeriti e l’espulsione dei residui non assorbiti. La gastrointestinal chemosensitivity è caratterizzata da elementi cellulari endocrini della mucosa gastroenterica e da fibre nervose, soprattutto di natura vagale. Una ampia gamma di mediatori endocrini e/o paracrini possono essere rilasciati da varie cellule endocrine in risposta a nutrienti introdotti con la dieta. Tali ormoni, oltre alla loro attività diretta, agiscono attraverso recettori specifici attivando azioni di assoluta importanza nel controllo di varie funzioni tra cui l’introito calorico e l’omeostasi energetica dell’organismo. Ad integrazione di questo complesso sistema di controllo della chemosensitività gastrointestinale, recenti evidenze dimostrano la presenza di recettori del gusto (o taste receptors, TR) appartenenti alla famiglia dei recettori correlati alle proteine G espressi a livello della mucosa del tratto gastrointestinale di diversi mammiferi e dell’uomo. La presente ricerca, suddivisa in diversi progetti di ricerca, è stata concepita al fine di chiarire il rapporto tra TR e nutrienti. Per definire questo rapporto sono stati usati diversi approcci scientifici, che sono andati a valutare le variazioni delle molecole segnale dei TR in particolare dell’α-transducina in condizioni di digiuno e a seguito di rialimentazione standard nel tratto gastrointestinale di suino, la mappatura della stessa molecola segnale nel tratto gastrointestinale di pesce (Dicentrarchus Labrax), il signaling pathway dei bitter TR in colture cellulari endocrine STC-1 ed infine il coinvolgimento dei bitter TR, in particolare del T2R38 in pazienti con un eccessivo introito calorico. I risultati hanno evidenziato come ci sia una stretta correlazione tra nutrienti, TR e rilascio ormonale e come questi siano coinvolti non solo nella percezione del gusto propriamente detto ma probabilmente anche in patologie croniche come l’obesità

Expression and regulation of α-transducin in the pig gastrointestinal tract

Taste signalling molecules are found in the gastrointestinal (GI) tract suggesting that they participate to chemosensing. We tested whether fasting and refeeding affect the expression of the taste signalling molecule, a-transducin (Gatran), throughout the pig GI tract and the peptide content of Gatran cells. The highest density of Gatran-immunoreactive (IR) cells was in the pylorus, followed by the cardiac mucosa, duodenum, rectum, descending colon, jejunum, caecum, ascending colon and ileum. Most Gatran-IR cells contained chromogranin A. In the stomach, many Gatran-IR cells contained ghrelin, whereas in the upper small intestine many were gastrin/cholecystokinin-IR and a few somatostatin-IR. Gatran-IR and Gagust-IR colocalized in some cells. Fasting (24 h) resulted in a significant decrease in Gatran-IR cells in the cardiac mucosa (29.3 0.8 versus 64.8 1.3, P < 0.05), pylorus (98.8 1.7 versus 190.8 1.9, P < 0.0 l), caecum (8 0.01 versus 15.5 0.5, P < 0.01), descending colon (17.8 0.3 versus 23 0.6, P < 0.05) and rectum (15.3 0.3 versus 27.5 0.7, P < 0.05). Refeeding restored the control level of Gatran-IR cells in the cardiac mucosa. In contrast, in the duodenum and jejunum, Gatran-IR cells were significantly reduced after refeeding, whereas Gatran-IR cells density in the ileum was not changed by fasting/refeeding. These findings provide further support to the concept that taste receptors contribute to luminal chemosensing in the GI tract and suggest they are involved in modulation of food intake and GI function induced by feeding and fasting

Caregiver burden and its related factors in advanced Parkinson’s disease: data from the PREDICT study

Introduction: Caring for a person with Parkinson’s disease (PD) is associated with an increased risk of psychiatric morbidity and persistent distress. The objective of this study was to describe the burden and the related factors of caregivers of advanced PD (APD) patients either treated with continuous dopaminergic delivery systems or standard therapy. Methods: This cross-sectional, epidemiologic study conducted in 13 Italian sites enrolled PD patients treated with continuous dopaminergic delivering systems [either levodopa/carbidopa intestinal gel (LCIG) infusion or continuous subcutaneous apomorphine infusion (CSAI)] or continuation of standard of care (SOC) with a caregiver. Patient quality of life (QoL) and caregiver burden were assessed using the Parkinson’s Disease Questionnaire (PDQ-8) and Zarit Burden Inventory (ZBI), respectively. Results: 126 patients (mean age 69.3 ± 8 years) and their caregivers (mean age 57.9 ± 12.9) were enrolled. Most caregivers were spouses. Fifty-three patients were treated with LCIG, 19 with CSAI, and 54 with SOC. Mean ZBI scores were 29.6 ± 14.4 for LCIG, 35.8 ± 20.2 for CSAI, and 31.4 ± 16.0 for SOC. Caregivers of LCIG, CSAI, and SOC patients showed no burden or mild/moderate burden in 74, 53, and 63% of the cases, respectively. Mean PDQ-8 scores were 11.25 ± 5.67, 11.26 ± 5.55, and 14.22 ± 6.51 in LCIG, CSAI, and SOC patients. Neurologists considered patients “very much or much improved” in 89, 58, and 13% of the LCIG, CSAI, and SOC groups using the Clinical Global Impression–Global Improvement Scale. Predictors significantly associated with caregiver burden were patients and caregivers’ judgment of QoL and caregivers’ need to change work. Conclusions: Caregiver burden showed a tendency to be lower when patients are treated with LCIG than with CSAI or SOC

CB1 Signaling in Forebrain and Sympathetic Neurons Is a Key Determinant of Endocannabinoid Actions on Energy Balance

SummaryThe endocannabinoid system (ECS) plays a critical role in obesity development. The pharmacological blockade of cannabinoid receptor type 1 (CB1) has been shown to reduce body weight and to alleviate obesity-related metabolic disorders. An unsolved question is at which anatomical level CB1 modulates energy balance and the mechanisms involved in its action. Here, we demonstrate that CB1 receptors expressed in forebrain and sympathetic neurons play a key role in the pathophysiological development of diet-induced obesity. Conditional mutant mice lacking CB1 expression in neurons known to control energy balance, but not in nonneuronal peripheral organs, displayed a lean phenotype and resistance to diet-induced obesity. This phenotype results from an increase in lipid oxidation and thermogenesis as a consequence of an enhanced sympathetic tone and a decrease in energy absorption. In conclusion, CB1 signaling in the forebrain and sympathetic neurons is a key determinant of the ECS control of energy balance

a-Transducin and a-gustducin immunoreactive cells in the stomach of common sole (Solea solea) fed with mussel meal

Vertebrates perceive a variety of exogenous substances using two main chemosensory systems, taste and olfaction. The taste perception occurs through the interaction of taste receptors associated with specific G protein subunits such as a-transducin (Gatran) and a-gustducin (Gagust). Aquatic vertebrates are also provided with a chemosensory system consisting of solitary chemosensory cells distributed to the oropharynx and skin. In this study, we identified Gatran and Gagust-immunoreactive cells intermingled with non-labeled epithelial cells in the gastric mucosa of the common sole. A long-term diet with increasing concentrations of mussel meal in the protein component of a conventional fish meal-based diet induced a dose-dependent increase in the gastric epithelial area and density of Gatran and Gagust immunoreactive cells. These findings suggest that taste-related molecules are regulated by changes in diet formulation in common sole aquaculture

Tumors of ampulla of Vater: A case series and review of chemotherapy options

Carcinomas of the Ampulla of Vater are rare tumors, accounting for 0.2% of gastrointestinal cancers. Compared with other biliary tract neoplasms, these tumors have a relatively favorable prognosis after surgical resection. Based on their epithelium of origin, two subtypes of ampullary carcinoma have been recently distinguished: intestinal and pancreatobiliary. This study evaluates histopathological features and outcomes of ampullary carcinoma and to compares the survival of these tumors to that of other biliary tract tumors. The chemotherapic options available for ampullary cancer are also reviewed. We analyzed data from 20 consecutive patients with ampullary carcinomas and 26 patients with other biliary tract carcinomas, observed in our Institution. Statistical analysis was performed by using either Fisher’s exact test or χ2 test for categorical variables. Median time of survival was calculated and compared using the Log-Rank test. Similar distribution of demographic characteristics and stage between ampullary and other biliary tract cancers was observed. Patients with ampullary cancer underwent surgery more frequently than other biliary cancers while chemotherapy and radiotherapy were used equally. In accordance with the literature, a longer median survival was observed in the group of ampullary carcinomas