Gastrointestinal targets to modulate satiety and food intake.

This review discusses the role of enteroendocrine cells in the gastrointestinal tract as chemoreceptors that sense intraluminal contents and induce changes in food intake through the release of signalling substances, such as satiety hormones. Recent evidence supports the concept that chemosensing in the gut involves G protein-coupled receptors (GPCRs) that are known to mediate gustatory signals in the oral cavity. GPCRs can be grouped into several families, depending on the stimuli to which they respond, e.g. proteins, amino acids, carbohydrates, fatty acids, or tastants. Sensing of these stimuli by GPCRs results in hormone secretions of enteroendocrine cells, which participate in the control of food intake. A better understanding of the stimuli that induce the strongest binding with these receptors, and thus induce a strong release of hormones, can be a very useful strategy for the development of novel foods in the treatment of obesity.

Peptide-YY is released by the intestinal cell line STC-1.

Dietary modulation of the response of gut satiety hormones, which partly regulate food intake, provides a promising treatment for overweight and obesity. Gut-derived cell lines such as STC-1 are widely used to investigate these hormonal responses to nutrients. To date, no peptide-YY (PYY) secreting cell line has been identified. The aim of this study was to investigate whether STC-1 cells are able to secrete PYY and if so, whether dietary compounds can modulate PYY secretion. The effects of fatty acid types C4:0, C12:0, C14:0, C16:0, and C18:0 on PYY release were investigated by measuring PYY in the supernatant after 30, 60, 90, and 120 min of incubation, respectively, using RIA assays. The STC-1 cells were able to secrete PYY in a time-dependent manner. It was shown that after 30 min, C4:0, C12:0, C16:0, and C18:0 caused increased PYY levels compared to the control. At time points 60 and 90 min, C4:0 and C18:0 induced elevated PYY levels compared to the control. After 120 min, C4:0, C14:0, and C18:0 caused elevated levels compared to the control. We are the first to show that the STC-1 cells are also able to secrete PYY next to cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1). Addition of fatty acids resulted in increased levels of PYY, which is consistent with the literature describing human studies. We conclude that the STC-1 cell line provides an appropriate cell line for screening the effects of ingredients on the release of the satiety-related gut hormones CCK, GLP-1, and PYY.

Diaphragm dysfunction in chronic obstructive pulmonary disease: a role for heparan sulphate?

In the present study, phage display-derived antibodies were used to investigate the topology of glycosaminoglycan epitopes in the diaphragm of chronic obstructive pulmonary disease (COPD) and non-COPD patients. Furthermore, the potential physiological significance of changes in the occurrence of glycosaminoglycan epitopes in the diaphragm of COPD patients was studied by determining the overlap in epitope recognition of glycosaminoglycan antibodies and growth factors. Diaphragm cryosections from non-COPD (n = 5) and COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II; n = 9) were incubated with antibodies directed against heparan sulphate, chondroitin sulphate and dermatan sulphate epitopes. Antibodies were visualised immunofluorescently. In addition, interference of antibody and growth factor binding with heparan sulphate epitopes was tested. Specific glycosaminoglycan epitopes showed increased expression in the diaphragm of COPD patients, whereas other epitopes were decreased or unaffected. Interestingly, the anti-heparan sulphate antibody HS4C3, which is directed against a downregulated epitope, interfered with the binding of hepatocyte growth factor. Three patients with the most severe airway obstruction also demonstrated interference of heparan sulphate antibody A04B08 with hepatocyte growth factor binding. Results indicate changes in glycosaminoglycan composition in the diaphragm of patients with chronic obstructive pulmonary disease. This may affect cellular physiology via alterations in growth factor handling and might be related to reduced levels of contractile protein in the diaphragm of these patients.