TY  - JOUR
AB  - Early-life programming is a major determinant of lifelong metabolic health, yet current preventive strategies focus almost exclusively on maternal factors. Emerging experimental and preclinical data reveal that a father's diet before conception, particularly high-fat intake, also shapes offspring physiology. Here, we synthesize the latest evidence on how such diets remodel the sperm epigenome during two discrete windows of vulnerability: (i) testicular spermatogenesis, via DNA methylation and histone modifications, and (ii) post-testicular epididymal maturation, where small non-coding RNAs are selectively gained. We examine how these epigenetic signals influence pregnancy, placental development, and ultimately, metabolic trajectories in progeny. To extend published work, we sourced publicly available diet-induced sperm epigenome datasets and provide new potential connections of these changes to genes governing placental development, vascularization and size using the International Mouse Phenotyping Consortium data. Moreover, we further interrogate these overlaps with intricate in-silico analyses to examine their potential consequences. To foster meaningful interactions with these findings, we have developed a web application for ease (ShinySpermPlacenta). Collectively, these findings support a biparental model of preconception care and position the sperm epigenome as a promising tractable biomarker platform for personalized paternal nutrition counselling aimed at improving fertility and reducing intergenerational metabolic disease risk.
AU  - Skerrett-Byrne, D.A.
AU  - Pepin, A.-S.
AU  - Laurent, K.
AU  - Beckers, J.
AU  - Schneider, R.
AU  - Hrabě de Angelis, M.
AU  - Teperino, R.
C1  - 75474
C2  - 57911
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Dad's diet shapes the future: How paternal nutrition impacts placental development and childhood metabolic health.
JO  - Mol. Nutr. Food Res.
PB  - Wiley
PY  - 2025
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - With the presentation of the blueprint of the first human genome in 2001 and the advent of technologies for high-throughput genetic analysis, personalized nutrition (PN) becomes a new scientific field and the first commercial offerings of genotype-based nutrition advice emerge at the same time. Here, the state of evidence for the effect of genetic and epigenetic factors in the development of obesity, the metabolic syndrome, and resulting illnesses such as non-insulin-dependent diabetes mellitus and cardiovascular diseases is summarized. This study also critically value the concepts of PN that are built around the new genetic avenue from both the academic and a commercial perspective and their effectiveness in causing sustained changes in diet, lifestyle, and for improving health. Despite almost 20 years of research and commercial direct-to-consumer offerings, evidence for the success of gene-based dietary recommendations is still generally lacking. This calls for new concepts of future PN solutions that incorporate more phenotypic measures and provide a panel of instruments (e.g., self- and bio-monitoring tools, feedback systems, algorithms based on artificial intelligence) that increases compliance based on the individual´s physical and social environment and value system.
AU  - Holzapfel, C.*
AU  - Waldenberger, M.
AU  - Lorkowski, S.*
AU  - Daniel, H.*
C1  - 65679
C2  - 52392
TI  - Genetics and epigenetics in personalized nutrition: Evidence, expectations, and experiences.
JO  - Mol. Nutr. Food Res.
VL  - 66
IS  - 17
PY  - 2022
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - SCOPE: It is unclear which factors influence the inter-individual variations of postprandial changes in blood glucose. Therefore, we investigated whether the habitual diet is associated with the postprandial glycemic response. METHODS AND RESULTS: Clinical and metabolic data from healthy adults (young adults with 18 - 25 years, middle-aged adults with 40 - 65 years, and older adults with 75 - 85 years) at baseline and during an oral glucose tolerance test (OGTT) was collected. Habitual diet was assessed by a food frequency questionnaire and two 24-hour food lists. Regression models were fitted to examine associations between habitual diet and glucose incremental area under the curve (iAUCmin ). The intake of cereals and cereal products is negatively associated with glucose iAUCmin (p  =  0.002) in the total cohort (N  =  459, 50 % women, 55 ± 21 years, BMI 26 ± 5 kg/m2 ). Total carbohydrate intake and the intake of cereals and cereal products predict glucose iAUCmin in the total cohort. Up to 9 % of the variance in the glycemic response was explained by the respective dietary parameters identified in the models of the specific age groups. CONCLUSION: These findings suggest, that there are age-specific diet-related effects on postprandial glucose response. Of all investigated dietary parameters, the usual intake of cereals and cereal products seems to play a greater role in postprandial glucose metabolism in more than one age group. Further research is needed, to establish how diet can be optimized based on age and the postprandial response. This article is protected by copyright. All rights reserved.
AU  - Reik, A.*
AU  - Brandl, B.*
AU  - Schauberger, G.*
AU  - Wawro, N.
AU  - Linseisen, J.
AU  - Skurk, T.*
AU  - Volkert, D.*
AU  - Hauner, H.*
AU  - Holzapfel, C.*
C1  - 65559
C2  - 52741
TI  - Association between habitual diet and the postprandial glucose response - an enable study.
JO  - Mol. Nutr. Food Res.
VL  - 66
IS  - 16
PY  - 2022
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - AIMS: The Optimal Fibre Trial investigated metabolic effects of insoluble cereal fibre in subjects with high-risk prediabetes. As the study shows dose-dependent moderate glycemic and anti-inflammatory benefits, especially in subjects with an obesity-related phenotype, the putative mechanism of action of this particular food component warrants clarification. A sub-group of the OptiFiT cohort received detailed body imaging throughout the study, permitting the analysis of effects on body fat distribution by fibre supplementation. METHODS: 180 Caucasian participants with impaired glucose tolerance (IGT) received a blinded, randomized supplementation with insoluble cereal fibre or placebo for two years. Once a year, all subjects underwent fasting blood sampling, oGTT and full anthropometric measurements. A subgroup of 47 subjects additionally provided data from magnetic resonance imaging and spectroscopy for quantification of adipose tissue distribution and liver fat content. We compare these outcomes between fibre and placebo group and assess mechanistic connections to improvements in glucose metabolism and inflammation. RESULTS: MR-assessed visceral and non-visceral body fat volume, fasting glucose, HbA1c, fasting insulin, insulin resistance and uric acid decreased in the fibre group, only. However, after adjustment for weight loss, there are no significant differences in changes of MR-derived measurements of body fat distribution between the intervention groups. There is a statistical trend for fibre-driven liver fat reduction in subjects with confirmed non-alcoholic fatty liver disease (NAFLD; n = 19). The entire MR subgroup shows the same pattern in metabolic improvements as the entire cohort. CONCLUSIONS: Data and evidence on beneficial effects of insoluble cereal fibre on visceral and hepatic fat storage is limited, but warrants further research. Targetted trials assessing the usefulness of fibre in visceral obesity and NAFLD are required.
AU  - Kabisch, S.*
AU  - Honsek, C.*
AU  - Kemper, M.*
AU  - Gerbracht, C.*
AU  - Meyer, N.T.M.*
AU  - Arafat, A.M.*
AU  - Birkenfeld, A.L.
AU  - Machann, J.
AU  - Dambeck, U.*
AU  - Osterhoff, M.A.*
AU  - Weickert, M.O.*
AU  - Pfeiffer, A.F.H.*
C1  - 61972
C2  - 50561
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Effects of insoluble cereal fibre on body fat distribution in the optimal fibre trial (OptiFiT).
JO  - Mol. Nutr. Food Res.
VL  - 65
IS  - 12
PB  - Wiley
PY  - 2021
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - Scope Alternaria fungi are widely distributed plant pathogens infecting grains and vegetables and causing major harvest losses in the field and during postharvest storage. Besides, consumers are endangered by the formation of toxic secondary metabolites. Some of these secondary metabolites are chemically characterized as mycotoxins, but the majority of the Alternaria mycobolome still remains unknown. Methods and results Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS) and LC-MS/MS are combined for the non-targeted and targeted analysis of the metabolome of three A. alternata isolates and one A. solani isolate. Due to the ultra-high resolution of FTICR-MS, unique molecular formulae are assigned to measured m/z signals. The molecular formulae are matched to entries of the databases Antibase and Kyoto Encyclopedia of Genes and Genomes. The non-targeted analysis of the fungal extracts reveals variations in the secondary metabolite profile of A. alternata and A. solani. Differences in the biosynthesis of dibenzo-alpha-pyrones, perylene quinones, tentoxin, and tenuazonic acid of the A. alternata and A. solani isolates are determined applying targeted LC-MS/MS. Conclusion FTICR-MS analyses reveal clear differences in the metabolic profile of the A. solani and the A. alternata isolates.
AU  - Gotthardt, M.*
AU  - Kanawati, B.
AU  - Schmidt, F.*
AU  - Asam, S.*
AU  - Hammerl, R.*
AU  - Frank, O.*
AU  - Hofmann, T.*
AU  - Schmitt-Kopplin, P.
AU  - Rychlik, M.*
C1  - 57525
C2  - 47833
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Comprehensive analysis of the Alternaria mycobolome using mass spectrometry based metabolomics.
JO  - Mol. Nutr. Food Res.
VL  - 64
IS  - 3
PB  - Wiley
PY  - 2020
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - Scope Effective treatment for obesity associated non-alcoholic fatty liver disease (NAFLD) is limited. Dietary supplementation of n-3 polyunsaturated fatty acids, specifically alpha linolenic acid (ALA), can resolve intrahepatic lipid content (IHL). This study investigates the effect of daily supplementation of either refined rapeseed (RA), containing high amounts of ALA, or refined olive (OL) oil on IHL and glucose metabolism in NAFLD patients. Methods and results 27 obese men consumed an isocaloric diet including either 50 g of RA or OL daily for 8 weeks. Hepatic proton magnetic resonance spectroscopy, hyperinsulinemic-euglycemic clamp studies and blood tests are performed before and at the end of the study. At 8 weeks a significant reduction in IHL is observed for RA (13.1 +/- 1.6 before versus 11.1 +/- 1.6% after intervention) versus OL (13.3 +/- 2.5 before versus 15.7 +/- 2.7% after intervention). For RA, a 21% reduction (P< 0.02) in serum free fatty acids (FFA) and a 1.68-fold increase (P= 0.03) of serum interleukin-6 (IL-6) is observed after 8 weeks. Conclusion RA has a beneficial effect on hepatic lipid metabolism as shown by reduced IHL and serum FFA. RA induced IL-6 production seems to be liver protective confirming previous results.
AU  - Kruse, M.*
AU  - Kemper, M.*
AU  - Gancheva, S.*
AU  - Osterhoff, M.*
AU  - Dannenberger, D.*
AU  - Markgraf, D.*
AU  - Machann, J.
AU  - Hierholzer, J.*
AU  - Roden, M.*
AU  - Pfeiffer, A.F.H.*
C1  - 60282
C2  - 49216
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Dietary rapeseed oil supplementation reduces hepatic steatosis in obese men-a randomized controlled trial.
JO  - Mol. Nutr. Food Res.
VL  - 64
IS  - 21
PB  - Wiley
PY  - 2020
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - Scope: Previous work identified three metabolically homogeneous subgroups of individuals (“metabotypes”) using k-means cluster analysis based on fasting serum levels of triacylglycerol, total cholesterol, HDL cholesterol, and glucose. The aim is to reproduce these findings and describe metabotype groups by dietary habits and by incident disease occurrence. Methods and results: 1744 participants from the KORA F4 study and 2221 participants from the KORA FF4 study are assigned to the three metabotype clusters previously identified by minimizing the Euclidean distances. In both KORA studies, the assignment of participants results in three metabolically distinct clusters, with cluster 3 representing the group of participants with the most unfavorable metabolic characteristics. Individuals of cluster 3 are further characterized by the highest incident disease occurrence during follow-up; they also reveal the most unfavorable diet with significantly lowest intakes of vegetables, dairy products, and fibers, and highest intakes of total, red, and processed meat. Conclusion: The three metabotypes originally identified in an Irish population are successfully reproduced. In addition to this validation approach, the observed differences in disease incidence across metabotypes represent an important new finding that strongly supports the metabotyping approach as a tool for risk stratification.
AU  - Riedl, A.
AU  - Hillesheim, E.*
AU  - Wawro, N.
AU  - Meisinger, C.
AU  - Peters, A.
AU  - Roden, M.*
AU  - Kronenberg, F.*
AU  - Herder, C.*
AU  - Rathmann, W.*
AU  - Voelzke, H.*
AU  - Reincke, M.*
AU  - Koenig, W.*
AU  - Wallaschofski, H.*
AU  - Daniel, H.*
AU  - Hauner, H*
AU  - Brennan, L.*
AU  - Linseisen, J.
C1  - 58883
C2  - 48415
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Evaluation of the metabotype concept identified in an Irish population in the German KORA cohort study.
JO  - Mol. Nutr. Food Res.
VL  - 64
IS  - 8
PB  - Wiley
PY  - 2020
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - Scope: "Metabotyping" describes the grouping of metabolically similar individuals. We aimed to identify valid metabotypes in a large cohort for targeted dietary intervention, for example, for disease prevention.Methods and results: We grouped 1729 adults aged 32-77 years of the German population-based KORA F4 study (2006-2008) using k-means cluster analysis based on 34 biochemical and anthropometric parameters. We identified three metabolically distinct clusters showing significantly different biochemical parameter concentrations. Cardiometabolic disease status was determined at baseline in the F4 study and at the 7 year follow-up termed FF4 (2013/2014) to compare disease prevalence and incidence between clusters. Cluster 3 showed the most unfavorable marker profile with the highest prevalence of cardiometabolic diseases. Also, disease incidence was higher in cluster 3 compared to clusters 2 and 1, respectively, for hypertension (41.2%/25.3%/18.2%), type 2 diabetes (28.3%/5.1%/2.0%), hyperuricemia/gout (10.8%/2.3%/0.7%), dyslipidemia (19.2%/18.3%/5.6%), all metabolic (54.5%/36.8%/19.7%), and all cardiovascular (6.3%/5.5%/2.3%) diseases together.Conclusion: Cluster analysis based on an extensive set of biochemical and anthropometric parameters allows the identification of comprehensive metabotypes that were distinctly different in cardiometabolic disease occurrence. As a next step, targeted dietary strategies should be developed with the goal of preventing diseases, especially in cluster 3.
AU  - Riedl, A.
AU  - Wawro, N.
AU  - Gieger, C.
AU  - Meisinger, C.
AU  - Peters, A.
AU  - Roden, M.*
AU  - Kronenberg, F.*
AU  - Herder, C.*
AU  - Rathmann, W.*
AU  - Völzke, H.*
AU  - Reincke, M.*
AU  - Koenig, W.*
AU  - Wallaschofski, H.*
AU  - Hauner, H.*
AU  - Daniel, H.*
AU  - Linseisen, J.
C1  - 54209
C2  - 45331
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Identification of comprehensive metabotypes associated with cardiometabolic diseases in the population-based KORA study.
JO  - Mol. Nutr. Food Res.
VL  - 62
IS  - 16
PB  - Wiley
PY  - 2018
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - ScopeOmega-3 polyunsaturated fatty acids (n-3 PUFA) found in fish oil activate PPAR-, stimulate peroxisomal fatty acid (FA) -oxidation and prevent impairments on glucose homeostasis. Methods and resultsGlucose metabolism and FA oxidation were studied in C57/Bl6 mice fed with diets containing either 3.6 and 31.5% fish oil or lard. To assess the effects of peroxisomal proliferation on FA oxidation independent of n-3 PUFA intake, mice were treated with the PPAR- agonist WY-14643. n-3 PUFA-fed mice were protected from glucose intolerance and dyslipidemia compared to animals fed a lard-based high-fat diet. Most importantly, mice fed on the hyperlipidic diet based on fish oil as well as the WY-14643 treated mice showed twofold increase of odd, medium-chain, dicarboxylic acylcarnitines in the liver suggesting that not only -oxidation, but also - and -oxidation of FA were increased. Finally, an oxidation assay using liver homogenates and palmitic acid as substrate revealed an over tenfold increased production of similar acylcarnitines, indicating that FA are their precursors. ConclusionThis study shows at the metabolite level that peroxisome proliferation induced either by fish oil or WY-14643 is associated with increased - and -oxidation of FA producing specific acylcarnitines that can be utilized as biomarkers of peroxisomal FA oxidation.
AU  - Fiamoncini, J.*
AU  - Lima, T.M.*
AU  - Hirabara, S.M.*
AU  - Ecker, J.
AU  - Gorjao, R.*
AU  - Romanatto, T.*
AU  - ELolimy, A.*
AU  - Worsch, S.
AU  - Laumen, H.
AU  - Bader, B.
AU  - Daniel, H.*
AU  - Curi, R.*
C1  - 46637
C2  - 37658
CY  - Hoboken
SP  - 1573-1583
TI  - Medium-chain dicarboxylic acylcarnitines as markers of n-3 PUFA-induced peroxisomal oxidation of fatty acids.
JO  - Mol. Nutr. Food Res.
VL  - 59
IS  - 8
PB  - Wiley-blackwell
PY  - 2015
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - SCOPE: Flaxseeds contain the phytoestrogens lignans that must be activated to enterolignans by intestinal bacteria. We investigated the impact of flaxseeds on fecal bacterial communities and their associations with fecal and blood metabolites. METHODS AND RESULTS: Nine healthy male adult subjects ingested 0.3 g/kg/d flaxseeds during one week. Gut bacteria as well as blood and fecal metabolites were analyzed. Ingestion of flaxseeds triggered a significant increase in the blood concentration of enterolignans, accompanied by fecal excretion of propionate and glycerol. Overall diversity and composition of dominant fecal bacteria remained individual-specific throughout the study. Enterolactone production was linked to the abundance of two molecular species identified as Ruminococcus bromii and Ruminococcus lactaris. Most dominant species of the order Bacteroidales were positively associated with fecal concentrations of either acetic, isovaleric, or isobutyric acid, the latter being negatively correlated with blood levels of triglycerides. The relative sequence abundance of one Gemmiger species (Ruminococcaceae) and of Coprococcus comes (Lachnospiraceae) correlated positively with blood levels of LDL-cholesterol and triglycerides, respectively. CONCLUSION: Flaxseeds increase enterolignan production but do not markedly alter dominant fecal metabolome and bacterial communities. The data underline the possible role of members of the family Ruminococcaceae in the regulation of enterolignan production and blood lipids.
AU  - Lagkouvardos, I.*
AU  - Kläring, K.*
AU  - Heinzmann, S.S.
AU  - Platz, S.*
AU  - Scholz, B.A.*
AU  - Engel, K.H.*
AU  - Schmitt-Kopplin, P.
AU  - Haller, D.*
AU  - Rohn, S.*
AU  - Skurk, T.*
AU  - Clavel, T.*
C1  - 44887
C2  - 37173
CY  - Hoboken
SP  - 1614–1628
TI  - Gut metabolites and bacterial community networks during a pilot intervention study with flaxseeds in healthy adult men.
JO  - Mol. Nutr. Food Res.
VL  - 59
IS  - 8
PB  - Wiley-blackwell
PY  - 2015
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics. Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale. Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.
AU  - Altmaier, E.
AU  - Kastenmüller, G.
AU  - Römisch-Margl, W.
AU  - Thorand, B.
AU  - Weinberger, K.M.*
AU  - Adamski, J.
AU  - Illig, T.
AU  - Döring, A.
AU  - Suhre, K.
C1  - 2263
C2  - 26539
SP  - 1357-1365
TI  - Variation in the human lipidome associated with coffee consumption as revealed by quantitative targeted metabolomics.
JO  - Mol. Nutr. Food Res.
VL  - 53
IS  - 11
PB  - Wiley-VCH
PY  - 2009
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - Studies in relatively small cohorts provide preliminary evidence that functional fatty acid binding protein 2 (FABP2) promoter haplotypes are associated with type 2 diabetes and BMI. Here, we studied the influence of the haplotypes on BMI by using 8072 male and female participants of the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) cohort. By linear regression analysis, we found in males a reduction of -0.39 BMI units (95% CI: -0.73, -0.05, p = 0.024) in homozygous FABP2 promoter haplotype B carriers. Carriers of haplotype B showed a significant decrease in BMI of -0.19 BMI units (95% CI: -0.35, -0.02, p = 0.027). In accordance, a significant reduction in BMI of the minor haplotype carriers in the BMI point categories of 25-30 (BMI units: -0.10, 95% CI: -0.18, -0.01, p = 0.03) and <30 (BMI units: -0.37, 95% CI: -0.67, -0.07, p = 0.02) were found. In summary, the minor FABP2 promoter haplotype B contributes to a reduced BMI in men. This provides evidence that functional FABP2 contributes to multifactorialy regulated body weight.
AU  - Böhme, M.*
AU  - Grallert, H.
AU  - Klapper, M.*
AU  - Gieger, C.
AU  - Fischer, A.*
AU  - Heid, I.M.
AU  - Wichmann, H.-E.
AU  - Döring, F.*
AU  - Illig, T.
C1  - 1222
C2  - 26991
SP  - 681-685
TI  - Association between functional FABP2 promoter haplotypes and body mass index: Analyses of 8072 participants of the KORA cohort study.
JO  - Mol. Nutr. Food Res.
VL  - 53
IS  - 6
PB  - Wiley-VCH
PY  - 2009
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - The human acyl-CoA-binding protein (ACBP) is a potential candidate gene of type 2 diabetes (T2D), since it plays a central role in determining the intracellular concentration of activated fatty acids which contribute to insulin resistance. The aim of our study was to evaluate whether single nucleotide polymorphisms (SNPs) of the ACBP gene are associated with risk of T2D. Genotyping of eight SNPs (rs2084202, rs3731607, rs8192501, rs8192504, rs2244135, rs2276596, rs8192506, rs2289948) was performed in 192 incident T2D subjects and 384 matched controls of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort. A putative promoter SNP (rs2084202) of splice variant ACBP 1c showed decreased risk of T2D (odds ratio (OR) 0.63, 95% CI 0.41-0.96). The haplotype, that contained the mutant base of rs2084202 showed similar evidence for the association with disease risk as single SNP rs2084202. In a second population-based study, Cooperative Health Research in the Augsburg Region of 226 individuals with T2D and 863 control subjects a borderline significant association between rs2084202 and T2D (OR 0.72, 95% CI 0.51-1.01) was observed. In summary, we obtained evidence from two Caucasian study populations that the minor allele of ACBP rs2084202 might be associated with reduced risk of T2D.
AU  - Fisher, E.*
AU  - Nitz, I.*
AU  - Gieger, C.
AU  - Grallert, H.
AU  - Gohlke, H.
AU  - Lindner, I.*
AU  - Dahm, S.*
AU  - Boeing, H.*
AU  - Burwinkel, B.*
AU  - Rathmann, W.*
AU  - Wichmann, H.-E.
AU  - Schrezenmeir, J.*
AU  - Illig, T.
AU  - Döring, F.*
C1  - 475
C2  - 24608
SP  - 178-184
TI  - Association of acyl-CoA-binding protein (ACBP) single nucleotide polymorphisms and type 2 diabetes in two German study populations.
JO  - Mol. Nutr. Food Res.
VL  - 51
IS  - 2
PB  - Wiley-VCH
PY  - 2007
SN  - 1613-4125
ER  - 

TY  - JOUR
AB  - Flavonoids are secondary plant metabolites included in our diet but are also provided in a growing number of supplements. They are suggested to interact with intestinal transport systems including phospho-glycoprotein (P-gp) which mediates the efflux of a variety of xenobiotics back into the gut lumen. In human intestinal Caco-2 cells, we tested the effects of 14 different flavonoids on P-gp expression in vitro. Protein expression levels were quantified by Western blotting, flow cytometry, and real-time PCR. Except apigenin, all flavonoids at concentrations of 10 M increased P-gp expression in Western blotting experiments when cells were exposed to the compounds over 4 wk. Flavone was one of the most effective P-gp inducers in Caco-2 cells and its effects were, therefore, also assessed for changes in P-gp in vivo in the gastrointestinal tract of C57BL/6 mice. P-gp expression was significantly increased by flavone (400 mg/kg body weight×day over 4 wk) in the small intestine but not in the colon which displayed intrinsically the highest expression level. In conclusion, the increase in P-gp expression caused by flavonoids in intestinal epithelial cells in vitro and also in vivo may serve as an adaptation and defense mechanism limiting the entry of lipophilic xenobiotics into the organism.
AU  - Lohner, K. *
AU  - Schnäbele, K.*
AU  - Daniel, H.*
AU  - Oesterle, D.
AU  - Rechkemmer, G.
AU  - Göttlicher, M.
AU  - Wenzel, U.*
C1  - 4988
C2  - 24420
SP  - 293-300
TI  - Flavonoids alter P-gp expression in intestinal epithelial cells in vitro and in vivo.
JO  - Mol. Nutr. Food Res.
VL  - 51
IS  - 3
PB  - Wiley-VCH
PY  - 2007
SN  - 1613-4125
ER  -