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The cashew allergens : a molecular and serological characterization
Reitsma, Marit - \ 2017
Wageningen University. Promotor(en): Harry Wichers; Huub Savelkoul, co-promotor(en): N.W. De Jong. - Wageningen : Wageningen University - ISBN 9789463430784 - 186
anacardium occidentale - allergens - serological surveys - protein transport - molecular detection - small intestine - pichia pastoris - in vivo experimentation - sds-page - western blotting - electrophoresis - allergenen - serologische overzichten - eiwittransport - moleculaire detectie - dunne darm - in vivo experimenten - elektroforese
Cashew nut allergy can be a severe food allergy of which the prevalence appears to be increasing. The aim of this thesis was a comprehensive molecular and serological characterisation of the cashew nut allergens Ana o 1, 2 and 3 for improved diagnosis and characterisation of patient populations.
Chapter 1 in this thesis provides background information on cashew nuts, allergy, the allergens Ana o 1, 2 and 3, the effect of heat treatments on cashew nut proteins, the digestibility of cashew nut proteins, cross-reactivity between cashew nut proteins and other tree nuts, and the detection of cashew nut in food products. Subsequently, in Chapter 2, a review is presented on the topic of epithelial protein and allergen transport. This review describes multiple pathways of intestinal protein transport, sums up existing experimental data concerning protein and peptide transport, and presents different methods to study this. Interestingly, the pathway of (allergenic) protein transport can differ between sensitized and non-sensitized persons. In sensitized persons, protein transport occurs transcellularly via enterocytes, and paracellularly with the involvement of mast cells, while in non-sensitized persons microfold cells and enterocytes are considered most important.
In the next three chapters, cashew nut allergens were studied. Cashew nut allergy and cashew nut allergens were chosen because of a high number of undiagnosed cashew nut allergic children reported at the children’s hospital “Kinderhaven”, in Rotterdam, an outpatient clinic that is involved in this study. Chapter 3 describes a protocol for the purification of Ana o 1, 2 and 3 from cashew nuts. Ana o 1 and 3 were purified by protein extraction, salt precipitation and filtering over a 30kDa molecular weight membrane. Ana o 2 was purified by protein extraction followed by gel filtration chromatography. These purified proteins were characterised by SDS-PAGE, western blot, glycoprotein stain, and protein identification. In this chapter also more in-depth analysis was performed on the N- and C-termini of the large and small subunits of Ana o 3. These N- and C-termini of Ana o 3, as well as the SDS-PAGE protein profiles were compared between cashew nuts of different origins in Chapter 4. In this chapter also the effects of different heat treatments on the electrophoretic behaviour of cashew nut allergens from various origins were studied, using both 1D and 2D electrophoresis. In these data no significant differences were detected between the electrophoresis patterns of Ana o 1, 2 or 3 in the various origins of cashew nuts. Some small but significant differences in Ana o 1, 2 and 3 content, however, were detected between the differently heated cashew nuts. No major differences in N- and C-terminal micro-heterogeneity were detected between cashew nuts of different origins.
Next, in Chapter 5, the cashew nut allergens Ana o 1, 2 and 3 were produced as recombinant proteins using a yeast (P. pastoris) production system. This procedure was used as recombinant allergens often produce higher yields of higher purity compared to native purified allergens. The recombinant proteins were compared to the native cashew nut proteins for their glycosylation pattern, IgE binding capacity, and 2D electrophoresis profile. In Chapter 6, the major findings of this thesis are discussed. An overview of the protein characteristics (e.g. 1D and 2D electrophoresis profile, glycosylation, IgE binding, pepsin-digestibility) was provided, as well as a discussion on the clinical benefits that can be derived from the results obtained in this thesis. Also some additional results are presented, studying the serologic cross-reactivity between cashew nuts and other tree nuts and Anacardiaceae nuts and fruits.
This thesis provides an in-depth study regarding the protein characteristics of the cashew nut allergens Ana o 1, 2 and 3. Using the allergens that were purified in this thesis project, the serum IgE levels of Ana o 1, 2 and 3 could be measured in cashew nut-allergic children. The allergens were also recombinantly produced to obtain higher quantity of allergens for regular use in diagnostics of cashew nut allergy. The results from this thesis can potentially expand clinical patient characterisation with measurements of IgE levels to purified and recombinantly produced major cashew nut allergens. These results might have applications for other food allergens or patient populations.
Small intestinal targets involved in food intake regulation : 'from nutrient to satiety signal'
Ripken, D. - \ 2016
Wageningen University. Promotor(en): Renger Witkamp; H.F.J. Hendriks. - Wageningen : Wageningen University - ISBN 9789462576438 - 180 p.
obesity - preventive nutrition - small intestine - ileum - duodenum - jejunum - satiety - appetite control - food intake - safflower oil - vagus nerve - casein - stevia rebaudiana - sucrose - macronutrients - serotonin - animal models - human feeding - obesitas - preventieve voeding - dunne darm - verzadigdheid - eetlustcontrole - voedselopname - saffloerolie - nervus vagus - caseïne - macronutriënten - serotonine - diermodellen - humane voeding
Background and aim: The worldwide increasing prevalence of overweight and obesity raises concerns for health. There is a clear need for preventive strategies, because current preventative interventions have proven to be unsuccessful in the long term. New strategies may be developed based on targets in the small intestine by activating satiety signals. The thesis aimed to investigate small intestinal targets contributing to food intake regulation. These targets included serotonin, the vagal nerve and the intestinal brake mechanism.
Methods: The effects of ileal stimulation with safflower oil (lipid mixture), casein (protein), sucrose (carbohydrate) and rebaudioside A (non-caloric sweetener) on GLP-1 and PYY release were investigated by applying an porcine ex vivo intestinal segment model. The same model was also used to investigate if serotonin is involved in (non-)nutritional-induced GLP-1 and PYY release.
The contribution to satiation of GLP-1 and CCK receptors at the vagal nerve, was studied by investigating the effects of GLP-1 and CCK receptor antagonists on ad libitum food intake in a pig model of subdiaphragmatic vagotomy.
Two placebo controlled randomized crossover studies were performed in healthy volunteers to investigate the effects of small intestinal macronutrient delivery on ad libitum food intake and satiety signals. The first study compared the effects of duodenal, jejunal and ileal casein delivery on ad libitum food intake and satiety signals. The second study investigated if ileal delivery of all three macronutrients results in activation of satiety signals and reduction in ad libitum food intake. In addition, it was investigated if ileal delivery of native casein is efficiently digested and absorbed and does not result in adverse effects. In both studies the nutrients were delivered to the small intestine by inserting a nasointestinal feeding tube in healthy volunteers.
Results: All macronutrients and rebaudioside A stimulated GLP-1 and PYY release from ileal tissue segments. Protein and fat stimulated serotonin release. Inhibiting the reuptake of serotonin resulted in enhanced nutrient induced GLP-1, PYY and CCK release. Serotonin stimulated GLP-1 release from enteroendocrine cells via a serotonin receptor mediated process.
Results of the in vivo pig study showed that antagonism of the CCK receptor increased food intake in both vagotomized and sham operated pigs. Blocking the GLP-1 receptor did not affect food intake in both groups.
The human studies showed that ileal protein delivery inhibited food intake and activated satiety signals as compared to duodenal or jejunal protein delivery. Also, ileal delivery of small quantities (51.7 kcal) of each macronutrient decreased food intake and activated satiety signals. In addition, it was shown that ileal delivery of native casein resulted in a time and concentration depended increase in plasma concentrations of amino acids and did not result in activation of immune responses nor in gastrointestinal complaints.
Conclusions: The data presented in this thesis show that ileal delivery of all macronutrients results in activation of satiety signals and reduction of food intake. Stimulation of the ileum resulted in the strongest activation of satiety signals and inhibition of food intake compared to duodenal and jejunal stimulation. Besides direct nutrient-receptor interaction, the ileum senses (non-)nutritional stimuli via serotonin mediated processes resulting in GLP-1 release. In conclusion, these results demonstrate that targeting the ileum with small amounts of macronutrients is safe and has potential as a weight management strategy.
Estimating requirements for apparent faecal and standardised ileal digestible amino acids in laying hens by a metaanalysis approach
Krimpen, M.M. van; Veldkamp, T. ; Riel, J.W. van; Khaksar, V. ; Hashemipour, H. ; Blok, M.C. ; Spek, W. - \ 2015
Wageningen : Wageningen UR Livestock Research (Livestock research report 848) - 71
hennen - aminozuren - voer - meta-analyse - verteerbaarheid - eiwitverteerbaarheid - dunne darm - voedingsstoffengehalte - voedingsstoffenbehoeften - voedingsbehoeften - pluimvee - pluimveevoeding - hens - amino acids - feeds - meta-analysis - digestibility - protein digestibility - small intestine - nutrient content - nutrient requirements - feed requirements - poultry - poultry feeding
The aim of the present study is to update the requirements for the essential amino acids of laying hens, both on a AFD and SID basis, by performing a meta-analysis on dose-response studies used to derive requirement values for essential amino acids (lysine, methionine+cysteine, threonine and tryptophan) in laying hens as presented in the literature. In this meta-analysis, the data are fitted by use of the Wood equation (see paragraph 2.4). The amino acid intake levels for realizing maximal rate of lay, egg mass and feed efficiency are provided. The amino acid requirements for use in practice are based on the amino acid intake levels at which 95% of these maximum responses were reached.
Copper in diets for weaned pigs : influence of level and duration of copper supplementation
Bikker, P. ; Baal, J. van; Binnendijk, G.P. ; Diepen, J.T.M. van; Troquet, L.M.P. ; Jongbloed, A.W. - \ 2015
Wageningen : Wageningen UR Livestock Research (Livestock Research report 830) - 38
varkens - biggen - spenen - koper - diervoedering - minerale supplementen - groei - dunne darm - voedertoevoegingen - biggenvoeding - pigs - piglets - weaning - copper - animal feeding - mineral supplements - growth - small intestine - feed additives - piglet feeding
This study was conducted to determine the influence of level (15-160 mg/kg voer)and period (2-8 weeks) of supply of a Cu-supplement on growth performance and expression of Cu absorption-related genes in different segments of the small intestine of weaned pigs.
Community and genomic analysis of the human small intestine microbiota
Bogert, B. van den - \ 2013
Wageningen University. Promotor(en): Michiel Kleerebezem, co-promotor(en): Erwin Zoetendal. - S.l. : s.n. - ISBN 9789461736628 - 214
darmmicro-organismen - dunne darm - dna microarrays - dna-sequencing - microbiële ecologie - immunomodulerende eigenschappen - intestinal microorganisms - small intestine - dna sequencing - microbial ecology - immunomodulatory properties
Our intestinal tract is densely populated by different microbes, collectively called microbiota, of which the majority are bacteria. Research focusing on the intestinal microbiota often use fecal samples as a representative of the bacteria that inhabit the end of the large intestine. These studies revealed that the intestinal bacteria contribute to our health, which has stimulated the interest in understanding their dynamics and activities. However, bacterial communities in fecal samples are different compared to microbial communities at other locations in the intestinal tract, such as the small intestine. Despite that the small intestine is the first region where our food and intestinal microbiota meet, we know little about the bacteria in the small intestine and how they influence our overall well-being. This is mainly attributable to difficulties in obtaining samples with the small intestine being located between the stomach and the large intestine. Therefore, the work in this thesis aimed at providing a better understanding of the composition and dynamics of the human small intestinal microbiota and to provide insight in the metabolic potential as well as immunomodulatory properties of some of its typical commensal inhabitants. Small intestinal samples used in the work described in this thesis were collected from ileostomy subjects, individuals that had their large intestine surgically removed and the end of the small intestine connected to an abdominal stoma, providing access to luminal content of the small intestine.
Considering the importance of molecular techniques in contemporary ecological surveys of microbial communities, first of all, two technologies, barcoded pyrosequencing and phylogenetic microarray analysis were compared in terms of their capacity to determine the bacterial composition in fecal and small intestinal samples from human individuals. As PCR remains a crucial step in sample preparation for both techniques, the use of different primer pairs in the amplification step was assessed in terms of its impact on the outcome of microbial profiling. The analyses revealed that the different primer pairs and the two profiling technologies provide overall similar results for samples of fecal and terminal ileum origin. In contrast, the microbial profiles obtained for small intestinal samples by barcoded pyrosequencing and phylogenetic microarray analysesdiffered considerably. This is most likely attributable to the constraints that are intrinsic to the use of the microarray to enable the detection of predefined microbiota members only, which is due to the probe design that is largely based on large intestinal microbiota communities. However, the pyrosequencing technology also allows for identification of bacteria that were not in advance known to inhabit our intestinal tract.
The pyrosequencing technology was used as the method of choice to study the total and active small intestinal communities in ileostoma effluent samples from four different subjects through sequencing the 16S ribosomal RNA gene (rDNA) and ribosomal RNA (rRNA) contentcombined with metatranscriptome analysis by Illumina sequencing of cDNA derived from enriched mRNAof the same sample set to investigate the activities of the small intestinal bacteria. The composition of the small intestinal bacterial communities as assessed from rDNA, rRNA, and mRNA patterns appeared to be similar, indicating that the dominant bacteria in the small intestine are also highly active in this ecosystem. Streptococcusspp. were among the bacterial species that were detected in each ileostoma effluent sample, albeit that their abundance varied greatly between samples from the same subject as well as samples from different subjects. Veillonellaspp. frequently co-occurred with Streptococcus spp., indicating that the Streptococcusand Veillonellapopulations play a prominent role in the human small intestine ecosystem and their co-occurrence suggests a metabolic relation between these genera.
Therefore, cultivation and molecular typing methodologies were employed to zoom-in on these groups, which revealed that the richness of the small intestinal streptococci strongly exceeded the diversity that could be estimated on basis of 16S rRNA analyses, and could be extended to the genomic lineage level (anticipated to resemble strain-level). From ileostoma samples 3 different Streptococcusspecies were recovered belonging to the S. mitisgroup, S. bovisgroup, and S. salivariusgroup, which could be further divided in 7 genomic lineages. Notably, the Streptococcuslineages that were isolated displayed distinct carbohydrate utilization capacities, which may imply that their growth and relative community composition may respond quite strongly to differences in the dietary intake of simple carbohydrates over time. This notion is in good agreement with the observation that the Streptococcuslineage populations fluctuated in time with only one Streptococcuslineage being cultivated from both ileostoma samples collected in a one-year time frame. Conversely, the cultivated Veillonellaisolates from samples during that same time-interval consistently encompassed a single lineage. Furthermore, this Veillonellalineage could be isolated from both the oral cavity as well as the ileostoma effluent. Analogously, three Streptococcuslineages that belong to a single phylotype also appeared to be present in bacterial communities from the oral cavity as well as the small intestine. These observations suggest the representatives of the Veillonellaand Streptococcusgenera that are encountered in the oral and small intestinal microbial ecosystems are closely related and indicate that the oral microbiota may serve as an inoculum for the upper GI tract.
The metabolic capacity of 6 small intestinal Streptococcus lineages, that were obtained from a single ileostoma effluent sample, was further investigated through the determination of genomic sequences of these lineages. The small-intestinal Streptococcusgenomes were found to encode different carbohydrate transporters and the necessary enzymes to metabolize different sugars, which was in excellent agreement with what carbohydrates could be used by representative strains of the Streptococcuslineages.
To further our understanding how the different streptococci as representatives of the dominant small intestinal bacterial populations may influence our immune system, human dendritic cells were stimulated with strains of the different Streptococcuslineages to study their immunomodulatory properties. The Streptococcuslineages differed significantly in their capacity to modulate cytokine responses of blood-monocyte derived immature dendritic cells. As Streptococcusand Veillonellafrequently co-occur in the small intestinal ecosystem, pair-wise combinations of strains of these two species were also tested for their combined immunomodulatory properties. This resulted in considerably different cytokine responses as those that could be predicted from the stimulations with either Streptococcusor Veillonella, indicating that it is not trivial to predict gut mucosal associated immune responses and thatthe composition of the intestinal microbiota as a whole may have a distinct influence on an individual’s immune status.
In conclusion, the work described this thesis provides an expansion to the accumulating knowledge on the human intestine microbiota. Whereas most studies focus on the microbiota present in the distal regions of the intestinal tract, this study targeted the microbiota of the poorly proximal regions of the intestine and also addressed its capacity to interact with the local mucosal tissue. The data presented here can be exploited to guide the design of future studies that aim to elucidate the interplay between diet, microbiota and the mucosal tissues in the human small intestinal tract.
Nutrition driven small-intestinal development and performance of weaned pigs and young broilers
Wijtten, P.J.A. - \ 2011
Wageningen University. Promotor(en): Martin Verstegen; Wouter Hendriks, co-promotor(en): H.B. Perdok. - S.l. : s.n. - ISBN 9789085859406 - 135
biggen - vleeskuikens - jonge dieren - dunne darm - ontogenie - diervoeding - voedingsstoffen - eiwitgehalte - prestatieniveau - dierlijke productie - piglets - broilers - young animals - small intestine - ontogeny - animal nutrition - nutrients - protein content - performance - animal production
The relative importance of animal husbandry and nutrition during the first weeks after weaning in pigs and after hatch in broilers has increased considerably over the past 50 years as a result of the tremendous improvement in daily body weight (BW) gain. Substantial changes in weight, architecture, and physiology of the small intestine occur early in the life of these animals. The optimal function of the small intestines is fundamental for nutrient absorption from the diet and for health. Nutrient requirement studies conducted on these animals have largely overlooked the very young animal. It is therefore logical that there are still gaps in our knowledge of the nutrition of these animals during this particular stage of life. The objective of this thesis was to improve small-intestinal development and performance of pigs after weaning and young broilers by ways of an optimal nutrient composition of the diet. In experiments with broilers, it was shown that enhanced dietary ideal protein (IP) concentrations in the starter diet increased BW gain in the starter phase and in the subsequent grower phase. Moreover, the effects of enhanced IP concentrations in the starter diet on BW gain are more marked than the effects in the grower and finisher diets. However, BW gain hardly improved in response to dietary IP increment during the first 3 d after hatch, whereas in the consecutive 3 d, BW gain improved substantially with enhanced dietary IP concentrations. This suggests that the first 3 d after hatch, from a nutritional point of view, are substantially different from the next consecutive days in the life of broiler chicks. Moreover, a 30% increase in dietary IP increased the duodenum weight between 6 and 9 d of age. Thus, in young broilers, a greater relative small-intestinal weight is associated with a greater BW gain. However, this thesis did not make a clear determination of the functional changes of the small intestine after hatch in broilers. A review of the literature showed that after weaning in pigs, the barrier function of the tight junctions of the small intestine is disturbed, and transcellular barrier function seems to improve after weaning. In the first study with pigs, the data here showed that paracellular barrier functions, as measured with orally administered lactulose, did not correlate with bacterial translocation or transcellular barrier function, as measured with horseradish peroxidase in Ussing chambers. Therefore, it was concluded that lactulose recovery in the urine of pigs after weaning is not associated with risk factors for infection. The last study with pigs showed that dietary protein with dextrose stimulates mucosal weight after weaning. However, the combination of protein with dextrose had no substantial effect on small-intestinal barrier function, whereas dietary starch with dextrose improved small-intestinal barrier function. In conclusion, optimising protein nutrition in broilers after hatch has a great potential to further improve overall broiler performance. In particular, knowledge regarding optimal nutrition during the first 3 d after hatch is still lacking. Furthermore, dietary protein is a potent stimulator for growth of the proximal small intestine in broilers and of the small-intestinal mucosa in pigs. However, mucosal mass and luminal protein are of minor importance for small-intestinal barrier function in pigs after weaning. In contrast, the luminal carbohydrate supply or energy level is important for maintaining small-intestinal barrier function.
Analysis of diversity and function of the human small intestinal microbiota
Booijink, C.C.G.M. - \ 2009
Wageningen University. Promotor(en): Willem de Vos; Michiel Kleerebezem; Erwin Zoetendal. - [S.l. : S.n. - ISBN 9789085853626 - 138
darmmicro-organismen - dunne darm - genexpressie - ileostomie - koolhydraatmetabolisme - metabolisme - microbiële diversiteit - functionele biodiversiteit - functionele genomica - genexpressieanalyse - intestinal microorganisms - small intestine - gene expression - ileostomy - carbohydrate metabolism - metabolism - microbial diversity - functional biodiversity - functional genomics - genomics
The gastrointestinal (GI) tract is the main site where the conversion and absorption of food components takes place in humans. As the small intestine is the first site of interaction between the microbiota and ingested food, knowledge about the microbial composition as well as functionality is essential for a complete understanding of the symbiotic interactions and to the potential modulation of metabolically important groups. Subjects carrying an ileostomy were chosen as model system and ileostomy effluent samples were collected over time. The diversity as well as activity of the inhabiting microbiota was analysed in ileostomy effluent samples of five healthy individuals, collected in the morning and afternoon over a period of 28 days. This revealed that the diversity of the ileostomy effluent microbiota was different from that in the faeces, mainly concerning the lower complexity and stability over time. In terms of composition the relative abundance of species belonging to the genera Streptococcus and Veillonella was higher, whereas a lower relative abundance of species related to the Ruminococcus obeum, R. gnavus and Bacteroides plebeius-like organisms was observed in ileostomy effluent samples. Marked differences in microbiota composition between the five subjects with an ileostomy were found, indicative for a highly personal ileal microbiota profile. Differences in microbiota composition profiles were observed over time, even visible within one day, although the overall fluctuations were around a relatively large stable core group, consisting of species belonging to three streptococci-related groups (S. bovis, S. intermedius and S. smitis), Clostridium cluster I, Enterococcus, Veillonella and Oxalobacter formigenes. Overall, the data presented in this thesis indicated that the genus Streptococcus is not only numerically abundant, but also predominates randomly generated metabolic activity profiles of the microbial ecosystem of the ileostomy effluent microbiota. Predominant functions exerted were related to metabolism, especially carbohydrate metabolism and transport. The fast transit of the ileal contents appears to generate an environment in which the capacity to rapidly metabolise the available carbohydrates is an important selective advantage.
Probing the role of PPAR alpha in the small intestine : a functional nutrigenomics approach
Bünger, M. - \ 2008
Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Guido Hooiveld. - [S.l.] : S.n. - ISBN 9789085049739 - 166
dunne darm - voedingsfysiologie - transcriptiefactoren - lipiden - lipidenabsorptie - nutrigenomica - small intestine - nutrition physiology - transcription factors - lipids - lipid absorption - nutrigenomics
Background The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor known for its control of metabolism in response to diet. Although functionally best characterized in liver, PPARα is also abundantly expressed in small intestine, the organ by which nutrients, including lipids, enter the body. Dietary fatty acids, formed during the digestion of triacylglycerols, are able to profoundly influence gene expression by activating PPARα. Since the average Western diet contains a high amount of PPARα ligands, knowledge on the regulatory and physiological role of PPARα in the small intestine is of particular interest.
Aim In this thesis the function of PPARα in the small intestine was studied using a combination of functional genomics experiments, advanced bioinformatics tools, and dietary intervention studies.
Results Detailed analyses on the expression of PPARα in small intestine showed that PPARα is most prominently expressed in villus cells of the jejunum, coinciding with the main anatomical location where fatty acids are digested and absorbed. Genome-wide transcriptome analysis in combination with feeding studies using the synthetic agonist WY14643 and several nutritional PPARα agonists revealed that PPARα controls processes ranging from fatty acid oxidation and cholesterol-, glucose- and bile acid metabolism to apoptosis and cell cycle. In addition, we connected PPARα with the intestinal immune system. In a more focussed study we showed that PPARα controls the barrier function of the intestine. By comparing the intestinal and hepatic PPARα transcriptome we found that PPARα controls in these two organs the expression of two distinct, but overlapping sets of genes. Finally, by performing a range of functional studies deduced from the transcriptome analysis, we demonstrated that PPARα controls intestinal lipid absorption.
Conclusion By maximally utilizing the unique possibilities offered in the post-genome era, the studies described in this thesis reported on the function of PPARα in small intestine. We conclude that intestinal PPARα plays an important role, is relevant for nutrition, and its effects are distinguishable from the hepatic PPARα response. Our results provide a better understanding of normal intestinal physiology, and may be of particular importance for the development of fortified foods, and prevention and therapies for treating obesity and inflammatory bowel diseases.
Regulation of small intestinal transport function by fatty acids and the role of PPAR alpha
Bosch, H.M. van den - \ 2008
Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Guido Hooiveld. - [S.l.] : S.n. - ISBN 9789085048664 - 190
dunne darm - biochemisch transport - transcriptiefactoren - vetzuren - agonisten - voedingsstoffentransport - small intestine - biochemical transport - transcription factors - fatty acids - agonists - nutrient transport
A key function of the small intestine is to form a selective barrier between the body and the environment. Potentially dangerous compounds and organisms have to be kept in the lumen, while simultaneously nutrients have to be taken up efficiently. Furthermore, the enterocyte is the first place where ingested toxic compounds are metabolized and directly excreted back into the gut lumen. The Western diet contains up to 40% of fat, mainly consisting of triacylglycerols. Unsaturated fatty acids are natural agonists for the transcription factor peroxisome proliferator- activated receptor alpha (PPARα), which among others is involved in regulation of lipid metabolism. In this thesis the effects of dietary lipids and the role of PPARα on small intestinal physiological processes was investigated, with special emphasis on nutrients, transporters and phase I/II metabolic enzymes. Therefore a nutrigenomics approach was applied using a PPARα-null mouse model.
The work described in this thesis demonstrates that PPARα is highly expressed in the small intestine. We characterized the function of PPARα by treatment with the synthetic agonist WY14643 and three different triacylglycerols, which when digested are natural PPARα agonists. We found that PPARα is important in regulating transport and phase I/II metabolism genes. PPARα-dependently regulated genes of this group were especially involved in fatty acid oxidation, cholesterol, glucose, and amino acid transport and metabolism, intestinal motility, and oxidative stress.
Furthermore we demonstrated that fasting induces an increased oxidation of fat and xenobiotics, increased cholesterol secretion, increased susceptibility to electrophilic stressors, and reduced intestinal motility. The role of PPARα in regulating fasting induced intestinal gene expression appeared not to be significant.
Finally, we showed that small intestinal cholesterol transporters were all down-regulated after a cholesterol-free, palm-oil based high-fat diet. We showed that these effects of dietary fatty acids are LXRα- and PPARα-independent. Our results suggest that on this diet cholesterol absorption is diminished and we speculate that cholesterol efflux is reduced to spare intracellular cholesterol for chylomicron formation.
Overall, the combined data from the various intervention studies clearly identified PPARα as an important transcriptional regulator in the small intestine, governing a multitude of cellular processes, including nutrient (metabolite) transport and phase I/II metabolism. However, detailed studies showed that the effects of dietary fatty acids on cholesterol uptake and metabolism are PPARα (and LXRα)-independent, demonstrating the complexity of nutrient-mediated gene expression.
Nutritional strategy affects gut wall integrity in weaned piglets
Verdonk, J.M.A.J. - \ 2006
Wageningen University. Promotor(en): Martin Verstegen, co-promotor(en): J. Huisman. - [S.l. ] : S.n. - ISBN 9085043468 - 153
biggen - spenen - melk - dunne darm - fysiologische functies - voeropname - maag - spijsvertering - morfologie - permeabiliteit - diervoeding - piglets - weaning - milk - small intestine - physiological functions - feed intake - stomach - digestion - morphology - permeability - animal nutrition
The role of the intestinal flora as affected by non-starch polysaccharides in broiler chicks
Langhout, D.J. - \ 1998
Agricultural University. Promotor(en): Martin Verstegen; S. Tamminga; J.B. Schutte. - S.l. : S.n. - ISBN 9789054859123 - 173
vleeskuikens - kippen - voer - viscositeit - polysacchariden - antinutritionele factoren - darmmicro-organismen - darmen - ileum - dunne darm - verteerbaarheid - pectinen - rogge - tarwe - broilers - fowls - feeds - viscosity - polysaccharides - antinutritional factors - intestinal microorganisms - intestines - small intestine - digestibility - pectins - rye - wheat
<p>It is well established that the non-starch polysaccharides (NSP) of wheat, rye and barley have anti-nutritive properties in broiler chicks. The water-soluble fraction of these NSP are assumed to be primary responsible for the anti-nutritive activity, producing depression in digestibility of nutrients and performance.</p><p>This study was undertaken to investigate the role of the intestinal microflora on the anti-nutritive properties of water-soluble NSP by using citrus pectin as model substrate. Citrus pectin is a highly fermentable NSP fraction of a viscous nature. Inclusion of high-methylated citrus pectin (HMC) in diets of young chicks resulted in a decreased nutrient digestibility and performance. This was associated with an increase of the microbial activity in the small intestine. In addition, ileal composition of the microflora and the morphology of the small intestinal wall was changed. Furthermore, degradation of conjugated bile acids was increased significantly by including HMC in the diet.</p><p>The effect of low-methylated citrus pectin (LMC) on these parameters was less pronounced than with HMC. When the HMC diet was fed to germ-free chicks, digestibility of nutrients and performance were hardly affected. It was concluded that the intestinal microflora mediates the magnitude of the anti-nutritive properties of water-soluble NSP in broiler chicks.</p>