A novel role for the extracellular matrix glycoprotein-Tenascin-X in gastric function.

KEY POINTS: Tenascin X (TNX) functions in the extracellular matrix of skin and joints where it maintains correct intercellular connections and tissue architecture TNX is associated exclusively with vagal-afferent endings and some myenteric neurones in mouse and human stomach, respectively. TNX-deficient mice have accelerated gastric emptying and hypersensitivity of gastric vagal mechanoreceptors that can be normalized by an inhibitor of vagal-afferent sensitivity. Cultured nodose ganglion neurones showed no changes in response to capsaicin, cholecystokinin and potassium chloride in TNX-deficient mice. TNX-deficient patients have upper gastric dysfunction consistent with those in a mouse model. Our translational studies suggest that abnormal gastric sensory function may explain the upper gut symptoms present in TNX deficient patients, thus making it important to study gastric physiology. TNX deficiency should be evaluated routinely in patients with connective tissue abnormalities, which will enable a better understanding of its role and allow targeted treatment. For example, inhibitors of vagal afferents-baclofen could be beneficial in patients. These hypotheses need confirmation via targeted clinical trials. ABSTRACT: Tenascin-X (TNX) is a glycoprotein that regulates tissue structure via anti-adhesive interactions with collagen in the extracellular matrix. TNX deficiency causes a phenotype similar to hypermobility Ehlers-Danlos syndrome involving joint hypermobility, skin hyperelasticity, pain and gastrointestinal dysfunction. Previously, we have shown that TNX is required for neural control of the bowel by a specific subtype of mainly cholinergic enteric neurones and regulates sprouting and sensitivity of nociceptive sensory endings in mouse colon. These findings correlate with symptoms shown by TNX-deficient patients and mice. We aimed to identify whether TNX is similarly present in neural structures found in mouse and human gastric tissue. We then determined whether TNX has a functional role, specifically in gastric motor and sensory function and nodose ganglia neurones. We report that TNX was present in calretinin-immunoreactive extrinsic nerve endings in mouse and human stomach. TNX deficient mice had accelerated gastric emptying and markedly increased vagal afferent responses to gastric distension that could be rescued with GABAB receptor agonist. There were no changes in nodose ganglia excitability in TNX deficient mice, suggesting that vagal afferent responses are probably the result of altered peripheral mechanosensitivity. In TNXB-deficient patients, significantly greater symptoms of reflux, indigestion and abdominal pain were reported. In the present study, we report the first role for TNX in gastric function. Further studies are required in TNX deficient patients to determine whether symptoms can be relieved using GABAB agonists

Development, characterization, and stability of O/W pepper nanoemulsions produced by high-pressure homogenization

Interest in the utilization of bioactive plant compounds in foods has increased due to their biochemical activities (antioxidant, antimicrobial, etc.), and as alternatives in the reduction of the use of high concentrations of chemical substances. However, some of these additives are hydrophobic, thus being harder to disperse into the food matrix, which is generally water-based. A good alternative is the use of low concentrations of these compounds as nanoemulsions. The objective of the present study was to develop oil-in-water nanoemulsions containing dedo-de-moça pepper extract for food applications. Research in the development of these nanoemulsions was carried out using a high-speed homogenizer, followed by a high-pressure homogenizer. The influence of the following parameters was assessed: type and concentration of surfactants, hidrophilic-lipophilic balance, lipid/aqueous phase ratio, surfactant/oil ratio, pepper extract composition in nanoemulsion, and processing conditions. Nanoemulsions were evaluated by environmental (centrifugal and thermal) and storage stabilities, characterized by average droplet size and -potential measurements, color, interfacial tension, atomic force, and cryo-scanning electron microscopy. Those with average droplet size between 132 ± 2.0 and 145 ± 1.0 nm were developed depending on working pressure and number of cycles; -potential was around 36.71 ± 0.62 mV and the best nanoemulsion was stable to centrifugation and most of the thermal stresses. Droplets were characterized with cryo-scanning electron microscopy as being spherical, homogeneous, and stable, and remained stable when stored at 4 °C and room temperature for over 120 days. The pepper nanoemulsion, developed in the present study, has potential applications in the food industry.The first author gratefully acknowledges the CNPq and CAPES (National Council for Scientific and Technological Development, Program Science without Boarder) for the BSWE^ PhD (Process 236877/2012-1) fellowship, and CAPES for the national PhD fellowship. The last author acknowledges the São Paulo Research Foundation (FAPESP) Brazil, for the grant (CEPID-FoRC, 2013/07914-8).info:eu-repo/semantics/publishedVersio

Altered gastric vagal mechanosensitivity in diet-induced obesity persists on return to normal chow and is accompanied by increased food intake

BACKGROUND AND AIMS: Gastric vagal afferents convey satiety signals in response to mechanical stimuli. The sensitivity of these afferents is decreased in diet-induced obesity. Leptin, secreted from gastric epithelial cells, potentiates the response of vagal afferents to mechanical stimuli in lean mice, but has an inhibitory effect in high-fat diet (HFD)-induced obese mice. We sought to determine whether changes in vagal afferent function and response to leptin in obesity were reversible by returning obese mice consuming a HFD to standard laboratory chow diet (SLD). METHODS: Eight-week-old female C57BL/6 mice were either fed a SLD (N=20) or HFD (N=20) for 24 weeks. A third group was fed a HFD for 12 weeks and then a SLD for a further 12 weeks (RFD, N=18). An in vitro gastro-oesophageal vagal afferent preparation was used to determine the mechanosensitivity of gastric vagal afferents and the modulatory effect of leptin (0.1–10 nM) was examined. Retrograde tracing and quantitative RT–PCR were used to determine the expression of leptin receptor (LepR) messenger RNA (mRNA) in whole nodose and specific cell bodies traced from the stomach. RESULTS: After 24 weeks, both the HFD and RFD mice had increased body weight, gonadal fat mass, plasma leptin, plasma insulin and daily energy consumption compared with the SLD mice. The HFD and RFD mice had reduced tension receptor mechanosensitivity and leptin further inhibited responses to tension in HFD, RFD but not SLD mice. Mucosal receptors from both the SLD and RFD mice were potentiated by leptin, an effect not seen in HFD mice. LepR expression was unchanged in the whole nodose, but was reduced in the mucosal afferents of the HFD and RFD mice. CONCLUSION: Disruption of gastric vagal afferent function by HFD-induced obesity is only partially reversible by dietary change, which provides a potential mechanism preventing maintenance of weight loss.S J Kentish, T A O'Donnell, C L Frisby, H Li, G A Wittert and A J Pag