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3. Associations of vitamin D status with dietary intakes and physical activity levels among adults from seven European countries: the Food4Me study

Author

Manios, Yannis, Moschonis, George, Lambrinou, Christina P., Mavrogianni, Christina, Tsirigoti, Lydia, Hoeller, Ulrich, Roos, Franz F., Bendik, Igor, Eggersdorfer, Manfred, Celis-Morales, Carlos, Livingstone, Katherine M., Marsaux, Cyril F. M., Macready, Anna L., Fallaize, Rosalind, O’Donovan, Clare B., Woolhead, Clara, Forster, Hannah, Walsh, Marianne C., Navas-Carretero, Santiago, San-Cristobal, Rodrigo, Kolossa, Silvia, Hallmann, Jacqueline, Jarosz, Mirosław, Surwiłło, Agnieszka, Traczyk, Iwona, Drevon, Christian A., van Ommen, Ben, Grimaldi, Keith, Matthews, John N. S., Daniel, Hannelore, Martinez, J. Alfredo, Lovegrove, Julie A., Gibney, Eileen R., Brennan, Lorraine, Saris, Wim H. M., Gibney, Mike, Mathers, John C., and on behalf of the Food4Me Study

Published
2018
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4. Circulating and adipose tissue immune cells in tissue‐specific insulin resistance in humans with overweight and obesity

Author

Trouwborst, Inez, primary, Wouters, Kristiaan, additional, Jocken, Johan W., additional, Jardon, Kelly M., additional, Gijbels, Anouk, additional, Dagnelie, Pieter C., additional, van Greevenbroek, Marleen M. J., additional, van der Kallen, Carla J., additional, Stehouwer, Coen D. A., additional, Schalkwijk, Casper G., additional, Richard, Nathalie, additional, Bendik, Igor, additional, Afman, Lydia A., additional, Blaak, Ellen E., additional, and Goossens, Gijs H., additional

Published
2023
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7. Circulating and adipose tissue immune cells in tissue-specific insulin resistance in humans with overweight and obesity

Author

Trouwborst, Inez, Wouters, Kristiaan, Jocken, Johan W., Jardon, Kelly M., Gijbels, Anouk, Dagnelie, Pieter C., van Greevenbroek, Marleen M.J., van der Kallen, Carla J., Stehouwer, Coen D.A., Schalkwijk, Casper G., Richard, Nathalie, Bendik, Igor, Afman, Lydia A., Blaak, Ellen E., Goossens, Gijs H., Trouwborst, Inez, Wouters, Kristiaan, Jocken, Johan W., Jardon, Kelly M., Gijbels, Anouk, Dagnelie, Pieter C., van Greevenbroek, Marleen M.J., van der Kallen, Carla J., Stehouwer, Coen D.A., Schalkwijk, Casper G., Richard, Nathalie, Bendik, Igor, Afman, Lydia A., Blaak, Ellen E., and Goossens, Gijs H.

Abstract

Objective: A proinflammatory adipose tissue (AT) microenvironment and systemic low-grade inflammation may differentially affect tissue-specific insulin sensitivity. This study investigated the relationships of abdominal subcutaneous AT (aSAT) and circulating immune cells, aSAT gene expression, and circulating inflammatory markers with liver and skeletal muscle insulin sensitivity in people with overweight and obesity. Methods: Individuals with overweight and obesity from the PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study (n = 219) and the Maastricht Study (replication cohort; n = 1256) underwent a seven-point oral glucose tolerance test to assess liver and muscle insulin sensitivity, and circulating inflammatory markers were determined. In subgroups, flow cytometry was performed to identify circulating and aSAT immune cells, and aSAT gene expression was evaluated. Results: The relative abundances of circulating T cells, nonclassical monocytes, and CD56dim CD16+ natural killer cells were inversely associated with liver, but not muscle, insulin sensitivity in the PERSON Study. The inverse association between circulating (classical) monocytes and liver insulin sensitivity was confirmed in the Maastricht Study. In aSAT, immune cell populations were not related to insulin sensitivity. Furthermore, aSAT gene expression of interleukin 6 and CD14 was positively associated with muscle, but not liver, insulin sensitivity. Conclusions: The present findings demonstrate that circulating immune cell populations and inflammatory gene expression in aSAT show distinct associations with liver and muscle insulin sensitivity.

Published
2023

8. Weekday sunlight exposure, but not vitamin D intake, influences the association between vitamin D receptor genotype and circulating concentration 25‐hydroxyvitamin D in a pan‐European population: the Food4Me study

Author

Livingstone, Katherine M., CelisMorales, Carlos, Hoeller, Ulrich, Lambrinou, Christina P., Moschonis, George, Macready, Anna L., Fallaize, Rosalind, Baur, Manuela, Roos, Franz F, Bendik, Igor, Grimaldi, Keith, NavasCarretero, Santiago, SanCristobal, Rodrigo, Weber, Peter, Drevon, Christian A., Manios, Yannis, Traczyk, Iwona, Gibney, Eileen R., Lovegrove, Julie A., Saris, Wim H., Daniel, Hannelore, Gibney, Mike, Martinez, J. Alfredo, Brennan, Lorraine, Hill, Tom R., and Mathers, John C.

Published
2017
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16. Vitamins, 5. Vitamin K

Author

Netscher, Thomas, primary, Bonrath, Werner, additional, Bendik, Igor, additional, Zimmermann, Peter‐Jan, additional, Weber, Fritz, additional, and Rüttimann, August, additional

Published
2020
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19. Two nuclear signalling pathways for vitamin D

Author

Carlberg, Carsten, Bendik, Igor, Wyss, Adrian, Meier, Elke, Sturzenbecker, Laurie J., Grippo, Joseph F., and Hunziker, Willi

Subjects
Vitamin D -- Physiological aspects, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Two distinct nuclear signalling pathways for vitamin D are activated respectively by the vitamin D receptor alone or in conjunction with the receptor's heterodimers and the retinoid-X receptor-alpha. An analysis of both Drosophila and mammalian cells was used to obtain these results that support the existence of two vitamin D response element classes.

Published
1993

20. Nuclear Retinoid Receptors and Their Mechanism of Action

Author

Pfahl, Magnus, primary, Apfel, Rainer, additional, Bendik, Igor, additional, Fanjul, Andrea, additional, Graupner, Gerhart, additional, Lee, Mi-Ock, additional, La-Vista, Nathalie, additional, Lu, Xian-Ping, additional, Piedrafita, Javier, additional, Ortiz, Maria Antonia, additional, Salbert, Gilles, additional, and Zhang, Xiao-Kun, additional

Published
1994
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21. Additional file 1: Figure S1. of Z-ligustilide and anti-inflammatory prostaglandins have common biological properties in macrophages and leukocytes

Author

Schwager, Joseph, Gagno, Lidia, Richard, Nathalie, Simon, Werner, Weber, Peter, and Bendik, Igor

Abstract

Viability of RAW 264.7 cells after incubation with graded amounts of ligustilide, EGCG, resveratrol, 15d–PGJ2 and rosiglitazone for 24 h. Figure S2. Regulation of inflammatory gene expression in RAW264.7 cells by ligustilide (25 μM) rosiglitazone (25 μM) and 15d–PGJ2 (2.5 μM). Table S1. Synopsis of effects on protein secretion by (murine) macrophages or peripheral blood leukocytes (human). Table S1. Sequences of primers and probes used in quantitative real-time PCR. Table S2. Comparison of effects of PGJ2 and ligustilide on cytokines and chemokine expression. (DOCX 465 kb)

Published
2018
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22. Vitamins, 3. Vitamin D

Author

Bendik, Igor, primary, Höller, Ulrich, additional, Marty, Maurus, additional, Schütz, Jan, additional, and Labler, Ludvik, additional

Published
2019
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23. The effects of polyphenol supplementation on adipose tissue morphology and gene expression in overweight and obese humans

Author

Most, Jasper, Warnke, Ines, Boekschoten, Mark V., Jocken, Johan W.E., de Groot, Philip, Friedel, Angelika, Bendik, Igor, Goossens, Gijs H., Blaak, Ellen E., Most, Jasper, Warnke, Ines, Boekschoten, Mark V., Jocken, Johan W.E., de Groot, Philip, Friedel, Angelika, Bendik, Igor, Goossens, Gijs H., and Blaak, Ellen E.

Abstract

Dietary polyphenols have beneficial effects on adipose tissue mass and function in rodents, but human studies are scarce. In a randomized, placebo-controlled study, 25 (10 women) overweight and obese humans received a combination of the polyphenols epigallocatechin-gallate and resveratrol (282 mg/d, 80 mg/d, respectively, EGCG+RES, n = 11) or placebo (PLA, n = 14) supplementation for 12 weeks. Abdominal subcutaneous adipose tissue (SAT) biopsies were collected for assessment of adipocyte morphology and micro-array analysis. EGCG+RES had no effects on adipocyte size and distribution compared with PLA. However, we identified pathways contributing to adipogenesis, cell cycle and apoptosis were significantly downregulated by EGCG+RES versus PLA. Furthermore, EGCG+RES significantly decreased expression of pathways related to energy metabolism, oxidative stress, inflammation, and immune defense as compared with PLA. In conclusion, the SAT gene expression profile indicates a reduced cell turnover after 12-week EGCG+RES in overweight-obese subjects. It remains to be elucidated whether these alterations translate into long-term metabolic effects.

Published
2018

24. Large-Scale Screening of Natural Products Transactivating Peroxisome Proliferator-Activated Receptor α Identifies 9S-Hydroxy-10E,12Z,15Z-Octadecatrienoic Acid and Cymarin as Potential Compounds Capable of Increasing Apolipoprotein A-I Transcription in Hum

Author

van der Krieken, Sophie E., primary, Popeijus, Herman E., additional, Bendik, Igor, additional, Böhlendorf, Bettina, additional, Konings, Maurice C. J. M., additional, Tayyeb, Jehad, additional, Mensink, Ronald P., additional, and Plat, Jogchum, additional

Published
2018
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27. Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice

Author

Grimaldi, Keith A., primary, van Ommen, Ben, additional, Ordovas, Jose M., additional, Parnell, Laurence D., additional, Mathers, John C., additional, Bendik, Igor, additional, Brennan, Lorraine, additional, Celis-Morales, Carlos, additional, Cirillo, Elisa, additional, Daniel, Hannelore, additional, de Kok, Brenda, additional, El-Sohemy, Ahmed, additional, Fairweather-Tait, Susan J., additional, Fallaize, Rosalind, additional, Fenech, Michael, additional, Ferguson, Lynnette R., additional, Gibney, Eileen R., additional, Gibney, Mike, additional, Gjelstad, Ingrid M. F., additional, Kaput, Jim, additional, Karlsen, Anette S., additional, Kolossa, Silvia, additional, Lovegrove, Julie, additional, Macready, Anna L., additional, Marsaux, Cyril F. M., additional, Alfredo Martinez, J., additional, Milagro, Fermin, additional, Navas-Carretero, Santiago, additional, Roche, Helen M., additional, Saris, Wim H. M., additional, Traczyk, Iwona, additional, van Kranen, Henk, additional, Verschuren, Lars, additional, Virgili, Fabio, additional, Weber, Peter, additional, and Bouwman, Jildau, additional

Published
2017
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28. Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial

Author

Most, Jasper, Most, Jasper, Timmers, Silvie, Warnke, Ines, Jocken, Johan W. E., van Boekschoten, Mark, de Groot, Philip, Bendik, Igor, Schrauwen, Patrick, Goossens, Gijs H., Blaak, Ellen E., Most, Jasper, Most, Jasper, Timmers, Silvie, Warnke, Ines, Jocken, Johan W. E., van Boekschoten, Mark, de Groot, Philip, Bendik, Igor, Schrauwen, Patrick, Goossens, Gijs H., and Blaak, Ellen E.

Abstract

Background: The obese insulin-resistant state is characterized by impairments in lipid metabolism. We previously showed that 3-d supplementation of combined epigallocatechin-3-gallate and resveratrol (EGCG+RES) increased energy expenditure and improved the capacity to switch from fat toward carbohydrate oxidation with a high-fat mixed meal (HFMM) test in men. Objective: The present study aimed to investigate the longer-term effect of EGCG+RES supplementation on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and tissue-specific insulin sensitivity. Design: In this randomized double-blind study, 38 overweight and obese subjects [18 men; aged 38 +/- 2 y; body mass index (kg/m(2)): 29.7 +/- 0.5] received either EGCG+RES (282 and 80 mg/d, respectively) or placebo for 12 wk. Before and after the intervention, oxidative capacity and gene expression were assessed in skeletal muscle. Fasting and postprandial (HFMM) lipid metabolism was assessed by using indirect calorimetry, blood sampling, and microdialysis. Tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with [6,6-H-2(2)]-glucose infusion. Results: EGCG+RES supplementation did not affect the fasting plasma metabolic profile. Although whole-body fat mass was not affected, visceral adipose tissue mass tended to decrease after the intervention compared with placebo (P-time X treatment = 0.09). EGCG+RES supplementation significantly increased oxidative capacity in permeabilized muscle fibers (P-time X treatment <0.05, P-EGCG+RES <0.05). Moreover, EGCG+RES reduced fasting (P-time X treatment = 0.03) and postprandial respiratory quotient (P-time X treatment = 0.01) compared with placebo. Fasting and postprandial fat oxidation was not significantly affected by EGCG +RES (P-EGCG+RES = 0.46 and 0.38, respectively) but declined after placebo (P-placebo = 0.05 and 0.03, respectively). Energy expenditure was not altered (P-time X treatment = 0.96). Furthermore, EGCG+R

Published
2016

29. Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial

Author

Most, Jasper, primary, Timmers, Silvie, additional, Warnke, Ines, additional, Jocken, Johan WE, additional, van Boekschoten, Mark, additional, de Groot, Philip, additional, Bendik, Igor, additional, Schrauwen, Patrick, additional, Goossens, Gijs H, additional, and Blaak, Ellen E, additional

Published
2016
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43. Transcriptome-Wide Profile of 25-Hydroxyvitamin D 3 in Primary Immune Cells from Human Peripheral Blood.

Author

Hanel, Andrea, Bendik, Igor, and Carlberg, Carsten

Abstract

Vitamin D3 is an essential micronutrient mediating pleiotropic effects in multiple tissues and cell types via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), which activates the transcription factor vitamin D receptor. In this study, we used peripheral blood mononuclear cells (PBMCs) obtained from five healthy adults and investigated transcriptome-wide, whether the precursor of 1,25(OH)2D3, 25-hydroxyvitamin D3 (25(OH)D3), has gene regulatory potential on its own. Applying thresholds of >2 in fold change of gene expression and <0.05 as a false discovery rate, in this ex vivo approach the maximal physiological concentration of 25(OH)D3 (250 nM (nmol/L)) none of the study participants had a significant effect on their PBMC transcriptome. In contrast, 1000 and 10,000 nM 25(OH)D3 regulated 398 and 477 genes, respectively, which is comparable to the 625 genes responding to 10 nM 1,25(OH)2D3. The majority of these genes displayed specificity to the tested individuals, but not to the vitamin D metabolite. Interestingly, the genes MYLIP (myosin regulatory light chain interacting protein) and ABCG1 (ATP binding cassette subfamily G member 1) showed to be specific targets of 10,000 nM 25(OH)D3. In conclusion, 100- and 1000-fold higher 25(OH)D3 concentrations than the reference 10 nM 1,25(OH)2D3 are able to affect the transcriptome of PBMCs with a profile comparable to that of 1,25(OH)2D3. [ABSTRACT FROM AUTHOR]

Published
2021
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44. Overexpression of Wnt target genes in adenomas of familial adenomatous polyposis patients.

Author

D'Orazio D, Muller PY, Heinimann K, Albrecht C, Bendik I, Herzog U, Tondelli P, Bauerfeind P, Müller H, and Dobbie Z

Subjects
Adenomatous Polyposis Coli metabolism, Adenomatous Polyposis Coli Protein biosynthesis, Adenomatous Polyposis Coli Protein genetics, Adolescent, Adult, Axin Protein, Cyclin D1 genetics, Cytoskeletal Proteins biosynthesis, Cytoskeletal Proteins genetics, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Proto-Oncogene Proteins c-myc genetics, Trans-Activators biosynthesis, Trans-Activators genetics, Wnt Proteins, beta Catenin, Adenomatous Polyposis Coli genetics, Cyclin D1 biosynthesis, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins c-myc biosynthesis, Zebrafish Proteins
Abstract

Germline mutations within the adenomatous polyposis coli (APC) gene, a key member of the Wnt signalling pathway, have been shown to cause adenoma development in familial adenomatous polyposis (FAP), a dominantly inherited predisposition to colorectal cancer. Although it has been suggested for several years that alterations within the Wnt pathway are the underlying events for the development of colorectal adenomas in FAP patients, no detailed analysis of the gene expressions of Wnt pathway members has been available in fresh colorectal tissue of FAP patients, so far. Thus, we investigated potential differences in the expressions of APC and its Wnt partners conductin, beta-catenin, cyclin D1, and c-myc in normal colorectal mucosa and matched adenoma tissue of 14 FAP patients using real-time quantitative PCR. The expressions of both Wnt target genes, cyclin D1 and c-myc, were significantly increased in adenoma compared to matched normal mucosa. Furthermore, the overexpressions of these two genes showed a highly significant positive correlation. Our data suggest that the concomitant overexpression of the Wnt targets and cell cycle regulators cyclin D1 and c-myc plays an important role in the neoplastic proliferation of adenomas in FAP patients.

Published
2002

45. Expression of COX-2 and Wnt pathway genes in adenomas of familial adenomatous polyposis patients treated with meloxicam.

Author

Dobbie Z, Muller PY, Heinimann K, Albrecht C, D'Orazio D, Bendik I, Müller H, and Bauerfeind P

Subjects
Adenomatous Polyposis Coli drug therapy, Adolescent, Adult, Cyclin D1 genetics, Cyclooxygenase 2, Female, Gene Expression Regulation, Neoplastic drug effects, Genes, APC drug effects, Genes, myc drug effects, Genes, myc genetics, Humans, Intestinal Mucosa drug effects, Intestinal Mucosa physiology, Male, Meloxicam, Membrane Proteins, Middle Aged, Protein-Tyrosine Kinases genetics, Rectal Neoplasms drug therapy, Rectal Neoplasms genetics, Reference Values, Reverse Transcriptase Polymerase Chain Reaction, Wnt Proteins, Adenomatous Polyposis Coli genetics, Antineoplastic Agents therapeutic use, Isoenzymes genetics, Prostaglandin-Endoperoxide Synthases genetics, Proto-Oncogene Proteins genetics, Thiazines therapeutic use, Thiazoles therapeutic use, Zebrafish Proteins
Abstract

Background: Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited predisposition to colorectal cancer caused by germline mutations within the adenomatous polyposis coli (APC) gene, a key member of the Wnt signalling pathway. A new class of non-steroidal anti-inflammatory drugs (NSAIDs), the specific cyclooxygenase 2 (COX-2) inhibitors, have recently been applied for the treatment of FAP patients., Patients and Methods: The expressions of the Wnt members and targets APC, c-myc, cyclin D1 and COX-2, as measured by real-time quantitative RT-PCR, have been evaluated in fresh samples of normal colorectal mucosa and matched adenoma tissue of six unrelated FAP patients before and after treatment with meloxicam., Results: A significant up-regulation of COX-2 in adenomas after treatment with meloxicam was found. Furthermore, in adenomas, a down-regulation of APC after treatment and a tight correlation of the expressions of the two Wnt targets, c-myc and cyclin D1, in both stages of treatment were observed., Conclusion: A feedback loop mediated by the peroxisome proliferator-activated receptor (PPAR) gamma is discussed as being responsible for the up-regulation of COX-2

Published
2002

46. Phytanic acid, a natural peroxisome proliferator-activated receptor (PPAR) agonist, regulates glucose metabolism in rat primary hepatocytes.

Author

Heim M, Johnson J, Boess F, Bendik I, Weber P, Hunziker W, and Fluhmann B

Subjects
Adipocytes cytology, Adipocytes drug effects, Animals, Biological Transport drug effects, Cell Differentiation, Cell Line, Cells, Cultured, Hepatocytes drug effects, Models, Biological, Protein Isoforms agonists, RNA, Messenger biosynthesis, Rats, Transcriptional Activation, Glucose metabolism, Hepatocytes metabolism, Hypoglycemic Agents pharmacology, Phytanic Acid pharmacology, Receptors, Cytoplasmic and Nuclear agonists, Transcription Factors agonists
Abstract

Phytanic acid, a metabolite of the chlorophyll molecule, is part of the human diet and is present in normal human serum at low micromolar concentrations. It was previously shown to be a ligand of the 9-cis-retinoic acid receptor and peroxisome proliferator-activated receptor (PPAR) a. PPAR agonists are widely used in the treatment of type 2 diabetes. Here, we report that phytanic acid is not only a transactivator of PPARa, but it also acts via PPARb and PPARg in CV-1 cells that have been cotransfected with the respective full-length receptor and an acyl-CoA oxidase-PPAR-responsive element-luciferase construct. We observed that, in contrast to other fatty acids, phytanic acid at physiological concentrations enhances uptake of 2-deoxy-D-glucose in rat primary hepatocytes. This result could be explained by the increase in mRNA expression of glucose transporters-1 and -2 and glucokinase, as determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Compared with the PPARg-specific agonist ciglitazone, phytanic acid exerts only minor effects on the differentiation of C3H10T1/2 cells into mature adipocytes. These results clearly demonstrate that phytanic acid acts via different PPAR isoforms to modulate expression of genes involved in glucose metabolism, thus suggesting a potential role of phytanic acid in the management of insulin resistance.

Published
2002
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