Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155μM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process.
Chinotto (Citrus myrtifolia Raf.) is a widely diffused plant native from China and its fruits have a wide-spread use in confectionary and drinks. Remarkably, only little has been reported thus far on its bioactive properties, in contrast to those of the taxonomically related bergamot (Citrus bergamia Risso). The present study aimed to investigate potential in vitro anti-inflammatory and radical scavenging properties of chinotto essential oils (CEOs) and to establish to what extent their composition and bioactivities are dependent on maturation. Essential oil from half ripe chinotto (CEO2) reduced the production of nitric oxide (NO) and the expression of inflammatory genes, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6), and chemokine monocyte chemotactic protein-1 (MCP-1) by lipopolysaccharide (LPS)-stimulated RAW264,7 macrophages. Limonene, linalool, linalyl acetate, and γ-terpinene were found to be the main components in CEO2. Moreover, CEO2 showed high radical scavenging activity measured as Trolox equivalents (TE) against both 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS). These findings show that chinotto essential oil represents a valuable part of this fruit and warrants further in vivo studies to validate its anti-inflammatory potential.
Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are hormones important for satiation and are involved in the process called "ileal brake". The aim of this study was to investigate the GLP-1- and PYY-stimulating efficacy of rebaudioside A, casein, and sucrose. This was studied using tissue segments collected from various regions of the pig small intestine. GLP-1 release was strongest from the distal ileum. There, control release was 0.06 ± 0.01 (GLP-1) and 0.07 ± 0.01 (PYY) pmol/cm(2) of tissue. Rebaudioside A (2.5, 12.5, and 25 mM) stimulated GLP-1 release (0.14 ± 0.02, 0.16 ± 0.02, and 0.13 ± 0.02 pmol/cm(2) of tissue, p < 0.001) and PYY release (0.19 ± 0.02, 0.42 ± 0.06, and 0.27 ± 0.03 pmol/cm(2) of tissue, p < 0.001). Sucrose stimulated GLP-1 release (0.08 ± 0.01 pmol/cm(2) of tissue, p < 0.05) only at 10 mM. Casein (0.5%, 1%, and 2.5%, w/v) stimulated GLP-1 release (0.15 ± 0.03, 0.13 ± 0.02, and 0.14 ± 0.01 pmol/cm(2) of tissue, p < 0.001) and PYY release (0.13 ± 0.02, 0.20 ± 0.03, and 0.27 ± 0.03 pmol/cm(2) of tissue, p < 0.01). These findings may help in developing dietary approaches for weight management.
Several mechanisms have been proposed for the positive health effects associated with dietary consumption of long-chain n -3 PUFA ( n -3 LC-PUFA) including DHA (22 : 6 n -3) and EPA (20 : 5 n -3). After dietary intake, LC-PUFA are incorporated into membranes and can be converted to their corresponding N -acylethanolamines (NAE). However, little is known on the biological role of these metabolites. In the present study, we tested a series of unsaturated NAE on the lipopolysaccharide (LPS)-induced NO production in RAW264.7 macrophages. Among the compounds tested, docosahexaenoylethanolamine (DHEA), the ethanolamide of DHA, was found to be the most potent inhibitor, inducing a dose-dependent inhibition of NO release. Immune-modulating properties of DHEA were further studied in the same cell line, demonstrating that DHEA significantly suppressed the production of monocyte chemotactic protein-1 (MCP-1), a cytokine playing a pivotal role in chronic inflammation. In LPS-stimulated mouse peritoneal macrophages, DHEA also reduced MCP-1 and NO production. Furthermore, inhibition was also found to take place at a transcriptional level, as gene expression of MCP-1 and inducible NO synthase was inhibited by DHEA. To summarise, in the present study, we showed that DHEA, a DHA-derived NAE metabolite, modulates inflammation by reducing MCP-1 and NO production and expression. These results provide new leads in molecular mechanisms by which DHA can modulate inflammatory processes.
