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1دورية أكاديمية
المؤلفون: Laurentya Olga, Ivana Bobeldijk-Pastorova, Richard C. Bas, Florine Seidel, Stuart G. Snowden, Samuel Furse, Ken K. Ong, Robert Kleemann, Albert Koulman
المصدر: STAR Protocols, Vol 3, Iss 4, Pp 101679- (2022)
مصطلحات موضوعية: Health sciences, Clinical protocol, Metabolism, Metabolomics, Mass spectrometry, Systems biology, Science (General), Q1-390
الوصف: Summary: This protocol outlines a translational lipidomic approach to discover lipid biomarkers that could predict morphometric body and histological organ measurements (e.g., weight and adiposity gains) during specific stages of life (e.g., early life). We describe procedures ranging from animal experimentation and histological analyses to downstream analytical steps through lipid profiling, both in mice and humans. This protocol represents a reliable and versatile approach to translate and validate candidate lipid biomarkers from animal models to a human cohort.For complete details on the use and execution of this protocol, please refer to Olga et al. (2021). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
وصف الملف: electronic resource
العلاقة: http://www.sciencedirect.com/science/article/pii/S2666166722005597Test; https://doaj.org/toc/2666-1667Test
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2دورية أكاديمية
المؤلفون: Eveline Gart, Kanita Salic, Martine C. Morrison, Martin Giera, Joline Attema, Christa de Ruiter, Martien Caspers, Frank Schuren, Ivana Bobeldijk-Pastorova, Marianne Heer, Yan Qin, Robert Kleemann
المصدر: Frontiers in Nutrition, Vol 9 (2022)
مصطلحات موضوعية: human milk oligosaccharides, prebiotics, non-alcoholic fatty liver disease, diacylglycerols, insulin resistance, obesity, Nutrition. Foods and food supply, TX341-641
الوصف: Non-alcoholic fatty liver disease (NAFLD) is a complex multifactorial disorder that is associated with gut dysbiosis, enhanced gut permeability, adiposity and insulin resistance. Prebiotics such as human milk oligosaccharide 2′-fucosyllactose are thought to primarily improve gut health and it is uncertain whether they would affect more distant organs. This study investigates whether 2′-fucosyllactose can alleviate NAFLD development in manifest obesity. Obese hyperinsulinemic Ldlr-/-.Leiden mice, after an 8 week run-in on a high-fat diet (HFD), were treated with 2′-fucosyllactose by oral gavage until week 28 and compared to HFD-vehicle controls. 2′-fucosyllactose did not affect food intake, body weight, total fat mass or plasma lipids. 2′-fucosyllactose altered the fecal microbiota composition which was paralleled by a suppression of HFD-induced gut permeability at t = 12 weeks. 2′-fucosyllactose significantly attenuated the development of NAFLD by reducing microvesicular steatosis. These hepatoprotective effects were supported by upstream regulator analyses showing that 2′-fucosyllactose activated ACOX1 (involved in lipid catabolism), while deactivating SREBF1 (involved in lipogenesis). Furthermore, 2′-fucosyllactose suppressed ATF4, ATF6, ERN1, and NUPR1 all of which participate in endoplasmic reticulum stress. 2′-fucosyllactose reduced fasting insulin concentrations and HOMA-IR, which was corroborated by decreased intrahepatic diacylglycerols. In conclusion, long-term supplementation with 2′-fucosyllactose can counteract the detrimental effects of HFD on gut dysbiosis and gut permeability and attenuates the development of liver steatosis. The observed reduction in intrahepatic diacylglycerols provides a mechanistic rationale for the improvement of hyperinsulinemia and supports the use of 2′-fucosyllactose to correct dysmetabolism and insulin resistance.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fnut.2022.904740/fullTest; https://doaj.org/toc/2296-861XTest
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3دورية أكاديمية
المؤلفون: Eveline Gart, Kanita Salic, Martine C. Morrison, Martien Caspers, Wim van Duyvenvoorde, Marieke Heijnk, Martin Giera, Ivana Bobeldijk-Pastorova, Jaap Keijer, Andreas B. Storsve, Petter-Arnt Hals, Robert Kleemann
المصدر: Nutrients, Vol 13, Iss 8, p 2836 (2021)
مصطلحات موضوعية: krill oil, polyunsaturated fatty acids (PUFAs), obesity, inflammation, oxylipins, adipogenesis, Nutrition. Foods and food supply, TX341-641
الوصف: The development of obesity is characterized by the metabolic overload of tissues and subsequent organ inflammation. The health effects of krill oil (KrO) on obesity-associated inflammation remain largely elusive, because long-term treatments with KrO have not been performed to date. Therefore, we examined the putative health effects of 28 weeks of 3% (w/w) KrO supplementation to an obesogenic diet (HFD) with fat derived mostly from lard. The HFD with KrO was compared to an HFD control group to evaluate the effects on fatty acid composition and associated inflammation in epididymal white adipose tissue (eWAT) and the liver during obesity development. KrO treatment increased the concentrations of EPA and DHA and associated oxylipins, including 18-HEPE, RvE2 and 14-HDHA in eWAT and the liver. Simultaneously, KrO decreased arachidonic acid concentrations and arachidonic-acid-derived oxylipins (e.g., HETEs, PGD2, PGE2, PGF2α, TXB2). In eWAT, KrO activated regulators of adipogenesis (e.g., PPARγ, CEBPα, KLF15, STAT5A), induced a shift towards smaller adipocytes and increased the total adipocyte numbers indicative for hyperplasia. KrO reduced crown-like structures in eWAT, and suppressed HFD-stimulated inflammatory pathways including TNFα and CCL2/MCP-1 signaling. The observed eWAT changes were accompanied by reduced plasma leptin and increased plasma adiponectin levels over time, and improved insulin resistance (HOMA-IR). In the liver, KrO suppressed inflammatory signaling pathways, including those controlled by IL-1β and M-CSF, without affecting liver histology. Furthermore, KrO deactivated hepatic REL-A/p65-NF-κB signaling, consistent with increased PPARα protein expression and a trend towards an increase in IkBα. In conclusion, long-term KrO treatment increased several anti-inflammatory PUFAs and oxylipins in WAT and the liver. These changes were accompanied by beneficial effects on general metabolism and inflammatory tone at the tissue level. The stimulation of adipogenesis by KrO allows for safe fat storage and may, together with more direct PPAR-mediated anti-inflammatory mechanisms, attenuate inflammation.
وصف الملف: electronic resource
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4دورية أكاديمية
المؤلفون: Kanita Salic, Eveline Gart, Florine Seidel, Lars Verschuren, Martien Caspers, Wim van Duyvenvoorde, Kari E. Wong, Jaap Keijer, Ivana Bobeldijk-Pastorova, Peter Y. Wielinga, Robert Kleemann
المصدر: International Journal of Molecular Sciences, Vol 20, Iss 18, p 4359 (2019)
مصطلحات موضوعية: obesity, non-alcoholic fatty liver disease, β-oxidation, mitochondria, metabolomics, acylcarnitines, transcriptomics, lipid peroxidation, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment with L-carnitine and nicotinamide riboside, i.e., components that can enhance fatty acid transfer across the inner mitochondrial membrane and increase nicotinamide adenine nucleotide (NAD+) levels, which are necessary for β-oxidation and the TCA cycle, respectively. Ldlr −/−.Leiden mice were treated with high-fat diet (HFD) supplemented with L-carnitine (LC; 0.4% w/w), nicotinamide riboside (NR; 0.3% w/w) or both (COMBI) for 21 weeks. L-carnitine plasma levels were reduced by HFD and normalized by LC. NR supplementation raised its plasma metabolite levels demonstrating effective delivery. Although food intake and ambulatory activity were comparable in all groups, COMBI treatment significantly attenuated HFD-induced body weight gain, fat mass gain (−17%) and hepatic steatosis (−22%). Also, NR and COMBI reduced hepatic 4-hydroxynonenal adducts. Upstream-regulator gene analysis demonstrated that COMBI reversed detrimental effects of HFD on liver metabolism pathways and associated regulators, e.g., ACOX, SCAP, SREBF, PPARGC1B, and INSR. Combination treatment with LC and NR exerts protective effects on metabolic pathways and constitutes a new approach to attenuate HFD-induced obesity and NAFLD.
وصف الملف: electronic resource
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5دورية أكاديمية
المؤلفون: Arianne van Koppen, Lars Verschuren, Anita M. van den Hoek, Joanne Verheij, Martine C. Morrison, Kelvin Li, Hiroshi Nagabukuro, Adalberto Costessi, Martien P.M. Caspers, Tim J. van den Broek, John Sagartz, Cornelis Kluft, Carine Beysen, Claire Emson, Alain J. van Gool, Roel Goldschmeding, Reinout Stoop, Ivana Bobeldijk-Pastorova, Scott M. Turner, Guido Hanauer, Roeland Hanemaaijer
المصدر: Cellular and Molecular Gastroenterology and Hepatology, Vol 5, Iss 1, Pp 83-98.e10 (2018)
مصطلحات موضوعية: Systems Biology, Metabolic Syndrome, Liver Disease, Diagnosis, Diseases of the digestive system. Gastroenterology, RC799-869
الوصف: The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis. Methods: A time-course study in low-density lipoprotein–receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis. An integrative systems biology approach was used to elucidate candidate markers linked to the active fibrosis process by combining transcriptomics, dynamic proteomics, and histopathology. The translational value of these findings were confirmed using human NASH data sets. Results: High-fat-diet feeding resulted in obesity, hyperlipidemia, insulin resistance, and NASH with fibrosis in a time-dependent manner. Temporal dynamics of key molecular processes involved in the development of NASH were identified, including lipid metabolism, inflammation, oxidative stress, and fibrosis. A data-integrative approach enabled identification of the active fibrotic process preceding histopathologic detection using a novel molecular fibrosis signature. Human studies were used to identify overlap of genes and processes and to perform a network biology-based prioritization to rank top candidate markers representing the early manifestation of fibrosis. Conclusions: An early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (pre)clinical experimental time frames.
وصف الملف: electronic resource
العلاقة: http://www.sciencedirect.com/science/article/pii/S2352345X17301479Test; https://doaj.org/toc/2352-345XTest
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6دورية أكاديمية
المؤلفون: Robert Kleemann, Marjan van Erk, Lars Verschuren, Anita M van den Hoek, Maud Koek, Peter Y Wielinga, Annie Jie, Linette Pellis, Ivana Bobeldijk-Pastorova, Thomas Kelder, Karin Toet, Suzan Wopereis, Nicole Cnubben, Chris Evelo, Ben van Ommen, Teake Kooistra
المصدر: PLoS ONE, Vol 5, Iss 1, p e8817 (2010)
الوصف: BACKGROUND: The sequence of events leading to the development of insulin resistance (IR) as well as the underlying pathophysiological mechanisms are incompletely understood. As reductionist approaches have been largely unsuccessful in providing an understanding of the pathogenesis of IR, there is a need for an integrative, time-resolved approach to elucidate the development of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Male ApoE3Leiden transgenic mice exhibiting a humanized lipid metabolism were fed a high-fat diet (HFD) for 0, 1, 6, 9, or 12 weeks. Development of IR was monitored in individual mice over time by performing glucose tolerance tests and measuring specific biomarkers in plasma, and hyperinsulinemic-euglycemic clamp analysis to assess IR in a tissue-specific manner. To elucidate the dynamics and tissue-specificity of metabolic and inflammatory processes key to IR development, a time-resolved systems analysis of gene expression and metabolite levels in liver, white adipose tissue (WAT), and muscle was performed. During HFD feeding, the mice became increasingly obese and showed a gradual increase in glucose intolerance. IR became first manifest in liver (week 6) and then in WAT (week 12), while skeletal muscle remained insulin-sensitive. Microarray analysis showed rapid upregulation of carbohydrate (only liver) and lipid metabolism genes (liver, WAT). Metabolomics revealed significant changes in the ratio of saturated to polyunsaturated fatty acids (liver, WAT, plasma) and in the concentrations of glucose, gluconeogenesis and Krebs cycle metabolites, and branched amino acids (liver). HFD evoked an early hepatic inflammatory response which then gradually declined to near baseline. By contrast, inflammation in WAT increased over time, reaching highest values in week 12. In skeletal muscle, carbohydrate metabolism, lipid metabolism, and inflammation was gradually suppressed with HFD. CONCLUSIONS/SIGNIFICANCE: HFD-induced IR is a time- and tissue-dependent process that starts in liver and proceeds in WAT. IR development is paralleled by tissue-specific gene expression changes, metabolic adjustments, changes in lipid composition, and inflammatory responses in liver and WAT involving p65-NFkB and SOCS3. The alterations in skeletal muscle are largely opposite to those in liver and WAT.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC2809107?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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7دورية أكاديمية
المؤلفون: Roman Hirseh, Thomas A. Ternes, Ivana Bobeldijk, Rudolf A. Week
المصدر: CHIMIA, Vol 55, Iss 1-2 (2001)
مصطلحات موضوعية: Environmental analysis, Fast gc, Spectral deconvolution, Tof-ms, Chemistry, QD1-999
الوصف: The use of GC/MS techniques is crucial to modern environmental trace analysis. However, due to the slow scanning capabilities of common quadrupole detectors, the implementation of fast gas chromatography is restricted. The now evolving Time-of-Flight mass detectors, have fast scanning capabilities and thus can provide the data density necessary to accurately define narrow chromatographic peaks typical for accelerated GC methods.The applications described herein demonstrate how the analysis of acidic pesticides and acidic drugs can be easily accelerated by a factor of 5 to 10 simply by using smaller column dimensions and higher helium flow rates. The quantitative data recorded with a Leco Pegasus II TOF system were comparable to the results obtained with the original routine methods. In addition to the fast acquisition, special software features allow peaks to be found automatically even when they are buried underneath the baseline, thus enabling an additional screening for unknown components besides the target analysis. A spectral deconvolution algorithm separates overlapping mass spectra and thus helps to deal with coeluting signals which can often be observed using fast GC conditions.
وصف الملف: electronic resource
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المؤلفون: Lisanne Pieters, Joanne M. Donkers, Esmée Wierenga, Ivana Bobeldijk, Tim Donkers, Joost Westerhout, Bastiaan Ingenhut, Irene Nooijen, Hossein Eslami Amirabadi, Lianne Stevens, Evita van der Steeg, Rosalinde Masereeuw
المساهمون: Group Den Toonder
المصدر: Lab on a Chip, 22(2), 326-342. Royal Society of Chemistry
مصطلحات موضوعية: Cell type, Swine, Chemistry, Microfluidics, Biomedical Engineering, Bioengineering, General Chemistry, Biochemistry, Permeability, Intestinal absorption, Cell Line, Cell biology, Intestines, chemistry.chemical_compound, Intestinal Absorption, Cell culture, Lactate dehydrogenase, Paracellular transport, Animals, Humans, Intestinal Mucosa, Transcellular, Intracellular, Explant culture
الوصف: The majority of intestinal in vitro screening models use cell lines that do not reflect the complexity of the human intestinal tract and hence often fail to accurately predict intestinal drug absorption. Tissue explants have intact intestinal architecture and cell type diversity, but show short viability in static conditions. Here, we present a medium throughput microphysiological system, Intestinal Explant Barrier Chip (IEBC), that creates a dynamic microfluidic microenvironment and prolongs tissue viability. Using a snap fit mechanism, we successfully incorporated human and porcine colon tissue explants and studied tissue functionality, integrity and viability for 24 hours. With a proper distinction of transcellular over paracellular transport (ratio >2), tissue functionality was good at early and late timepoints. Low leakage of FITC-dextran and preserved intracellular lactate dehydrogenase levels indicate maintained tissue integrity and viability, respectively. From a selection of low to high permeability drugs, 6 out of 7 properly ranked according to their fraction absorbed. In conclusion, the IEBC is a novel screening platform benefitting from the complexity of tissue explants and the flow in microfluidic chips.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::285dfc6213e97ee29ae5f914bb73eff0Test
https://doi.org/10.1039/d1lc00669jTest -
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المؤلفون: Jeanette Erdmann, Heribert Schunkert, Marijke Bijker-Schreurs, Ivana Bobeldijk-Pastorova, Lisette de Jong, Jan Albert Kuivenhoven, Alain J. van Gool
المصدر: Drug Discovery Today, 4, 25, 787-492
Drug Discovery Today, 25, 4, pp. 787-792
Drug Discovery Today, 25, 787-792مصطلحات موضوعية: 0301 basic medicine, Pharmacology, Biomedical Research, business.industry, Cardiovascular research, MEDLINE, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Public relations, RISK LOCI, Europe, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Drug Development, Work (electrical), Cardiovascular Diseases, 030220 oncology & carcinogenesis, Drug Discovery, Humans, Molecular Targeted Therapy, business, Disease treatment, Independent research
الوصف: Research consortia in Europe often compete with each other for skills, human and technical resources and, eventually, recognition of the scientific impact of their work. In response to the same EU Horizon2020 call, we received funding for our research project proposals to identify and validate novel drug targets for cardiovascular disease treatment. Each consortium followed a unique and independent research strategy. However, as coordinators of these consortia we envisioned we could increase impact, outcomes and efficiency by intensifying our interaction. At an agreed stage during our projects we chose to share our knowledge, vision and ideas. In this paper we present what we learned, in the hope that future consortia will see the benefits of this approach.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a82536fdb6c077b3d8f625bcd3087cfeTest
https://doi.org/10.1016/j.drudis.2020.01.009Test -
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المؤلفون: Rosalind Davies, Janna A. van Diepen, Lauren R. Brink, Sabina Bijlsma, Karen‐Anne McVey Neufeld, John F. Cryan, Siobhain M. O'Mahony, Ivana Bobeldijk, Gabriele Gross
المصدر: Molecular Nutrition & Food Research (Formerly Nahrung/Food), 66
Molecular Nutrition & Food Research (Formerly Nahrung/Food), 66, 22مصطلحات موضوعية: Brain, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Lipid Droplets, Blood plasma, Rodents, Rats, Sphingomyelins, Rats, Sprague-Dawley, Mice, Milk fat globule membrane, Dietary Supplements, Lipidomics, Animals, Glycolipids, Phospholipids, Glycoproteins, Food Science, Biotechnology
الوصف: Scope: Milk fat globule membrane (MFGM) is an essential component of milk. Bovine MFGM (bMFGM) has been shown to support cognitive development and increase relative concentrations of serum phospholipids. This study investigated bioavailability of bMFGM components after oral administration in two preclinical models to explore whether dietary bMFGM induced parallel changes to plasma and brain lipidomes. Methods and results: Transgenic APOE*3.Leiden mice (n = 18/group) and Sprague-Dawley rats (n = 12/group) were fed bMFGM-enriched (MFGM+) or Control diet, after which phospholipid profiles were determined in peripheral plasma, hippocampus and prefrontal cortex tissue by targeted mass spectrometry. Multivariate analysis of lipidomic profiles demonstrated a clear separation between MFGM+ and Control plasma samples across rodents. In plasma, sphingomyelins contributed the most to the separation of lipid patterns among both models, where three sphingomyelins (d18:1/14:0, d18:1/23:0, d18:1/23:1[9Z]) were significantly and consistently higher in the circulation of MFGM+ versus Control groups. A similar trend was observed in rat prefrontal cortex, although no significant separation of the brain lipidome was demonstrated. Conclusion: bMFGM-enriched diet alters plasma phospholipid composition in rodents, predominantly increasing sphingomyelin levels in the systemic circulation with some similar, but non-significant, trends in central regions of the brain. These changes may contribute to the beneficial effects of dietary bMFGM on neurodevelopment during early life.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bb5cbab6372446fd741b4ef3689a810dTest
https://doi.org/10.1002/mnfr.202200177Test
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