Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.

Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells) and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP) technique) to study the effect of food compounds. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies

The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Obesity and insulin resistance are two major risk factors underlying the metabolic syndrome. The development of these metabolic disorders is frequently studied, but mainly in liver, skeletal muscle, and adipose tissue. To gain more insight in the role of the small intestine in development of obesity and insulin resistance, dietary fat-induced differential gene expression was determined along the longitudinal axis of small intestines of C57BL/6J mice.</p> <p>Methods</p> <p>Male C57BL/6J mice were fed a low-fat or a high-fat diet that mimicked the fatty acid composition of a Western-style human diet. After 2, 4 and 8 weeks of diet intervention small intestines were isolated and divided in three equal parts. Differential gene expression was determined in mucosal scrapings using Mouse genome 430 2.0 arrays.</p> <p>Results</p> <p>The high-fat diet significantly increased body weight and decreased oral glucose tolerance, indicating insulin resistance. Microarray analysis showed that dietary fat had the most pronounced effect on differential gene expression in the middle part of the small intestine. By overrepresentation analysis we found that the most modulated biological processes on a high-fat diet were related to lipid metabolism, cell cycle and inflammation. Our results further indicated that the nuclear receptors Ppars, Lxrs and Fxr play an important regulatory role in the response of the small intestine to the high-fat diet. Next to these more local dietary fat effects, a secretome analysis revealed differential gene expression of secreted proteins, such as Il18, Fgf15, Mif, Igfbp3 and Angptl4. Finally, we linked the fat-induced molecular changes in the small intestine to development of obesity and insulin resistance.</p> <p>Conclusion</p> <p>During dietary fat-induced development of obesity and insulin resistance, we found substantial changes in gene expression in the small intestine, indicating modulations of biological processes, especially related to lipid metabolism. Moreover, we found differential expression of potential signaling molecules that can provoke systemic effects in peripheral organs by influencing their metabolic homeostasis. Many of these fat-modulated genes could be linked to obesity and/or insulin resistance. Together, our data provided various leads for a causal role of the small intestine in the etiology of obesity and/or insulin resistance.</p

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance:an individual-patient- and sequence-level meta-analysis

Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.status: publishe

The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice-8

Ance test was performed after 7 weeks of diet intervention. After an oral gavage of 100 mg glucose, blood glucose levels were monitored for 150 minutes. The changes in blood glucose levels (upper figure) and the area under he curve were calculated (lower figure). In (A) and (B), data are means ± SE. * p < 0.05. LF = low-fat diet, HF = high-fat diet.<p><b>Copyright information:</b></p><p>Taken from "The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice"</p><p>http://www.biomedcentral.com/1755-8794/1/14</p><p>BMC Medical Genomics 2008;1():14-14.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2396659.</p><p></p

The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice-5

Ined after 2 weeks of low-fat diet intervention. qPCR data of the nuclear receptors are visualized as the mean expression of individual mice ± SE. Expression in the middle and distal part of the small intestine is relative to the expression in the proximal part, which was set to 1. , , and indicate significant (p < 0.05, two-tailed Student's test) differential gene expression between the distinct parts of the small intestine (between the proximal and middle part, between the middle and distal part and between the proximal and distal part).<p><b>Copyright information:</b></p><p>Taken from "The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice"</p><p>http://www.biomedcentral.com/1755-8794/1/14</p><p>BMC Medical Genomics 2008;1():14-14.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2396659.</p><p></p

The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice-6

Of nuclear (hormone) receptors and their target genes was determined by microarray analysis, after 2, 4, and 8 weeks of high-fat diet intervention. Red and green boxes indicate a significant up- and down-regulation, respectively. NC = no change, A = absent.<p><b>Copyright information:</b></p><p>Taken from "The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice"</p><p>http://www.biomedcentral.com/1755-8794/1/14</p><p>BMC Medical Genomics 2008;1():14-14.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2396659.</p><p></p

The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice-0

Ance test was performed after 7 weeks of diet intervention. After an oral gavage of 100 mg glucose, blood glucose levels were monitored for 150 minutes. The changes in blood glucose levels (upper figure) and the area under he curve were calculated (lower figure). In (A) and (B), data are means ± SE. * p < 0.05. LF = low-fat diet, HF = high-fat diet.<p><b>Copyright information:</b></p><p>Taken from "The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice"</p><p>http://www.biomedcentral.com/1755-8794/1/14</p><p>BMC Medical Genomics 2008;1():14-14.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2396659.</p><p></p