Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Regulation of endoplasmic reticulum-mitochondria contacts and mitochondrial dynamics by Sel1L-Hrd1 ERAD during thermogenesis
    Zhou, Zhangsen ; Torres, Mauricio ; Sha, Haibo ; Halbrook, Christopher J. ; Bergh, Françoise van den; Reinert, Rachel B. ; Yamada, Tatsuya ; Wang, Siwen ; Luo, Yingying ; Hunter, Allen H. ; Wang, Chunqing ; Sanderson, Thomas H. ; Liu, Meilian ; Taylor, Aaron ; Sesaki, Hiromi ; Lyssiotis, Costas A. ; Wu, Jun ; Kersten, Sander ; Beard, Daniel A. ; Qi, Ling - \ 2020
    Wageningen University
    GSE145895 - PRJNA608688 - Mus musculus
    Organelles such as endoplasmic reticulum (ER) and mitochondria interact with each other at specialized domains on the ER known as mitochondria-associated membranes (MAMs). Here, using three-dimensional high-resolution imaging techniques, we show that the Sel1LHrd1 protein complex, the most conserved branch of ER-associated protein degradation (ERAD), exerts a profound impact on ER-mitochondria contacts and mitochondrial dynamics, at least in part, by regulating the turnover and hence the abundance of the MAM protein sigma receptor 1 (SigmaR1). Sel1L or Hrd1 deficiency in brown adipocytes impairs dynamic interaction between ER and mitochondria, leading to the formation of pleomorphic “megamitochondria” and, in some cases with penetrating ER tubule(s), in response to acute cold challenge. Mice with ERAD deficiency are cold sensitive and exhibit mitochondrial dysfunction in brown adipocytes. Mechanistically, endogenous SigmaR1 is targeted for proteasomal degradation by Sel1L-Hrd1 ERAD, whose accumulation in ERAD-deficient cells leads to mitofusin 2 (Mfn2) oligomerization, thereby linking ERAD to mitochondrial dynamics. Our study identifies Sel1L-Hrd1 ERAD as a critical determinant of ER-mitochondria contacts, thereby regulating mitochondrial dynamics and thermogenesis.
    Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes
    Zhou, Zhangsen ; Torres, Mauricio ; Sha, Haibo ; Halbrook, Christopher J. ; Bergh, Françoise van den; Reinert, Rachel B. ; Yamada, Tatsuya ; Wang, Siwen ; Luo, Yingying ; Hunter, Allen H. ; Wang, Chunqing ; Sanderson, Thomas H. ; Liu, Meilian ; Taylor, Aaron ; Sesaki, Hiromi ; Lyssiotis, Costas A. ; Wu, Jun ; Kersten, Sander ; Beard, Daniel A. ; Qi, Ling - \ 2020
    Science 368 (2020)6486. - ISSN 0036-8075 - p. 54 - 60.

    The endoplasmic reticulum (ER) engages mitochondria at specialized ER domains known as mitochondria-associated membranes (MAMs). Here, we used three-dimensional high-resolution imaging to investigate the formation of pleomorphic “megamitochondria” with altered MAMs in brown adipocytes lacking the Sel1L-Hrd1 protein complex of ER-associated protein degradation (ERAD). Mice with ERAD deficiency in brown adipocytes were cold sensitive and exhibited mitochondrial dysfunction. ERAD deficiency affected ER-mitochondria contacts and mitochondrial dynamics, at least in part, by regulating the turnover of the MAM protein, sigma receptor 1 (SigmaR1). Thus, our study provides molecular insights into ER-mitochondrial cross-talk and expands our understanding of the physiological importance of Sel1L-Hrd1 ERAD.

    Impact of One-Health framework on vaccination cost-effectiveness: A case study of rabies in Ethiopia
    Beyene, Tariku Jibat ; Fitzpatrick, Meagan C. ; Galvani, Alison P. ; Mourits, Monique C.M. ; Revie, Crawford W. ; Cernicchiaro, Natalia ; Sanderson, Michael W. ; Hogeveen, Henk - \ 2019
    One Health 8 (2019). - ISSN 2352-7714
    Cost-effectiveness - Ethiopia - Modeling - One-health - Rabies

    Livestock losses due to rabies and health and the corresponding benefits of controlling the disease are not often considered when the cost-effectiveness of rabies control is evaluated. In this research, assessed the benefits of applying a One Health perspective that includes these losses to the case of canine rabies vaccination in Ethiopia. We constructed a dynamic epidemiological model of rabies transmission. The model was fit to district-specific data on human rabies exposures and canine demography for two districts with distinct agro-ecologies. The epidemiological model was coupled with human and livestock economic outcomes to predict the health and economic impacts under a range of vaccination scenarios. The model indicates that human exposures, human deaths, and rabies-related livestock losses would decrease monotonically with increasing vaccination coverage. In the rural district, all vaccination scenarios were found to be cost-saving compared to the status quo of no vaccination, as more money could be saved by preventing livestock losses than would be required to fund the vaccination campaigns. Vaccination coverages of 70% and 80% were identified as most likely to provide the greatest net health benefits at the WHO cost-effectiveness threshold over a period of 5 years, in urban and rural districts respectively. Shorter time frames led to recommendations for higher coverage in both districts, as did even a minor threat of rabies re-introduction. Exclusion of rabies-related livestock losses reduced the optimal vaccination coverage for the rural district to 50%. This study demonstrated the importance of including all economic consequences of zoonotic disease into control decisions. Analyses that include cattle and other rabies-susceptible livestock are likely better suited to many rural communities in Africa wishing to maximize the benefits of canine vaccination.

    The Native Oyster Restoration Alliance (NORA) and the Berlin Oyster Recommendation: bringing back a key ecosystem engineer by developing and supporting best practice in Europe
    Pogoda, Bernadette ; Brown, Janet ; Hancock, Boze ; Preston, Joanne ; Pouvreau, Stephane ; Kamermans, Pauline ; Sanderson, William ; Nordheim, Henning von - \ 2019
    Aquatic Living Resources 32 (2019). - ISSN 0990-7440 - 9 p.
    Ostrea edulis - Berlin oyster recommendation - biogenic reef - ecosystem service - biodiversity
    Efforts to restore the native oyster Ostrea edulis and its associated habitats are gaining momentum across Europe. Several projects are currently running or being planned. To maximize the success of these, it is crucial to draw on existing knowledge and experience in order to design, plan and implement
    restoration activities in a sustainable and constructive approach. For the development of best practice recommendations and to promote multidimensional knowledge and technology exchange, the Native Oyster
    Restoration Alliance (NORA) was formed by partners from science, technology, nature conservation, consultancies, commercial producers and policy-makers. The NORA network will enhance scientific and practical progress in flat oyster restoration, such as in project planning and permitting, seed oyster production, disease management and monitoring. It also focuses on joint funding opportunities and the potential development of national and international regulatory frameworks. The main motivation behind NORA is to facilitate the restoration of native oyster habitat within its historic biogeographic range in the
    North Sea and other European seas along with the associated ecosystem services; services such as enhancing biodiversity, including enhanced fish stocks, nutrient cycling and sediment stabilization. NORA members agreed on a set of joint recommendations and strongly advise that any restoration measure should respect and apply these recommendations: The Berlin Oyster Recommendation is presented here. It will help guide the development of the field by developing and applying best practice accordingly. NORA also aims to
    combine the outreach activities of local projects for improved community support and awareness and to provide educational material to increase knowledge of the key ecological role of this species and increase awareness among regulators, permit providers and stakeholders. A synthesis of O. edulis restoration efforts in Europe is provided and underlines the general significance in the field.
    Insect community composition and functional roles along a tropical agricultural production gradient
    Bellamy, Angelina Sanderson ; Svensson, Ola ; Den Brink, Paul J. van; Gunnarsson, Jonas ; Tedengren, Michael - \ 2018
    Environmental Science and Pollution Research 25 (2018)14. - ISSN 0944-1344 - p. 13426 - 13438.
    Banana production - Costa Rica - Ecosystem services - Functional roles - Insect diversity - Management practices
    High intensity agricultural production systems are problematic not only for human health and the surrounding environment, but can threaten the provision of ecosystem services on which farm productivity depends. This research investigates the effects of management practices in Costa Rica on on-farm insect diversity, using three different types of banana farm management systems: high-input conventional system, low-input conventional system, and organic system. Insect sampling was done using pitfall and yellow bowl traps, left for a 24-h period at two locations inside the banana farm, at the edge of the farm, and in adjacent forest. All 39,091 individual insects were classified to family level and then morphospecies. Insect species community composition and diversity were compared using multivariate statistics with ordination analysis and Monte Carlo permutation testing, and revealed that each of the management systems were significantly different from each other for both trap types. Insect diversity decreased as management intensity increased. Reduced insect diversity resulted in fewer functional groups and fewer insect families assuming different functions essential to ecosystem health. Organic farms had similar species composition on the farm compared to adjacent forest sites, whereas species composition increasingly differed between farm and forest sites as management intensity increased. We conclude that while organic production has minimal impact on insect biodiversity, even small reductions in management intensity can have a significantly positive impact on on-farm insect biodiversity and functional roles supported.
    Assessing the ecological impact of banana farms on water quality using aquatic macroinvertebrate community composition
    Svensson, Ola ; Bellamy, Angelina Sanderson ; Brink, Paul J. Van Den; Tedengren, Michael ; Gunnarsson, Jonas S. - \ 2018
    Environmental Science and Pollution Research 25 (2018)14. - ISSN 0944-1344 - p. 13373 - 13381.
    In Costa Rica, considerable effort goes to conservation and protection of biodiversity, while at the same time agricultural pesticide use is among the highest in the world. Several protected areas, some being wetlands or marine reserves, are situated downstream large-scale banana farms, with an average of 57 pesticide applications per year. The banana industry is increasingly aware of the need to reduce their negative environmental impact, but few ecological field studies have been made to evaluate the efficiency of proposed mitigation strategies. This study compared the composition of benthic macroinvertebrate communities up- and downstream effluent water from banana farms in order to assess whether benthic invertebrate community structure can be used to detect environmental impact of banana farming, and thereby usable to assess improvements in management practises. Aquatic invertebrate samples were collected at 13 sites, using kick-net sampling, both up- and downstream banana farms in fast flowing streams in the Caribbean zone of Costa Rica. In total, 2888 invertebrate specimens were collected, belonging to 15 orders and 48 families or taxa. The change in community composition was analysed using multivariate statistics. Additionally, a biodiversity index and the Biological Monitoring Working Party (BMWP) score system was applied along with a number of community composition descriptors. Multivariate analyses indicated that surface waters immediately up- and downstream large-scale banana farms have different macroinvertebrate community compositions with the most evident differences being higher dominance by a single taxa and a much higher total abundance, mostly of that same taxon. Assessment of macroinvertebrate community composition thus appears to be a viable approach to detect negative impact from chemical-intensive agriculture and could become an effective means to monitor the efficacy of changes/proposed improvements in farming practises in Costa Rica and similar systems.
    Extending miscanthus cultivation with novel germplasm at six contrasting sites
    Kalinina, Olena ; Nunn, Christopher ; Sanderson, Ruth ; Hastings, Astley F.S. ; Weijde, Tim van der; Özgüven, Mensure ; Tarakanov, Ivan ; Schüle, Heinrich ; Trindade, Luisa M. ; Dolstra, Oene ; Schwarz, Kai Uwe ; Iqbal, Yasir ; Kiesel, Andreas ; Mos, Michal ; Lewandowski, Iris ; Clifton-Brown, John C. - \ 2017
    Frontiers in Plant Science 8 (2017). - ISSN 1664-462X
    Establishment - Marginal land - Miscanthus - Multi-location field trials - Novel hybrids - Productivity

    Miscanthus is a genus of perennial rhizomatous grasses with C4 photosynthesis which is indigenous in a wide geographic range of Asian climates. The sterile clone, Miscanthus × giganteus (M. × giganteus), is a naturally occurring interspecific hybrid that has been used commercially in Europe for biomass production for over a decade. Although, M. × giganteus has many outstanding performance characteristics including high yields and low nutrient offtakes, commercial expansion is limited by cloning rates, slow establishment to a mature yield, frost, and drought resistance. In this paper, we evaluate the performance of 13 novel germplasm types alongside M. × giganteus and horticultural “Goliath” in trials in six sites (in Germany, Russia, The Netherlands, Turkey, UK, and Ukraine). Mean annual yields across all the sites and genotypes increased from 2.3 ± 0.2 t dry matter ha−1 following the first year of growth, to 7.3 ± 0.3, 9.5 ± 0.3, and 10.5 ± 0.2 t dry matter ha−1 following the second, third, and fourth years, respectively. The highest average annual yields across locations and four growth seasons were observed for M. × giganteus (9.9 ± 0.7 t dry matter ha−1) and interspecies hybrid OPM-6 (9.4 ± 0.6 t dry matter ha−1). The best of the new hybrid genotypes yielded similarly to M. × giganteus at most of the locations. Significant effects of the year of growth, location, species, genotype, and interplay between these factors have been observed demonstrating strong genotype × environment interactions. The highest yields were recorded in Ukraine. Time needed for the crop establishment varied depending on climate: in colder climates such as Russia the crop has not achieved its peak yield by the fourth year, whereas in the hot climate of Turkey and under irrigation the yields were already high in the first growing season. We have identified several alternatives to M. × giganteus which have provided stable yields across wide climatic ranges, mostly interspecies hybrids, and also Miscanthus genotypes providing high biomass yields at specific geographic locations. Seed-propagated interspecific and intraspecific hybrids, with high stable yields and cheaper reliable scalable establishment remain a key strategic objective for breeders.

    What is in a label? Rainforest-Alliance certified banana production versus non-certified conventional banana production
    Bellamy, Angelina Sanderson ; Svensson, Ola ; Brink, Paul J. van den; Tedengren, Michael - \ 2016
    Global Ecology and Conservation 7 (2016). - ISSN 2351-9894 - p. 39 - 48.
    Banana production - Costa Rica - Insect diversity - Management practices - Rainforest Alliance certification

    Export banana production in Latin America is pesticide intensive, receiving much negative publicity regarding human health problems and environmental degradation. The Rainforest Alliance (RA) certification scheme was established to certify farms that met a number of social, occupation health and environmental standards set by RA and their certifying body, the Sustainable Agriculture Network (SAN). This study was one of the first, independent studies of the environmental impact of some of the principles set by RA and SAN. The study focuses on insect and bird diversity as an indicator of ecosystem health. Five RA certified farms, six non-RA certified farms, and five organic certified farms were sampled. The data was analyzed with RDA multivariate analyses and Monte Carlo permutation tests. The results showed that RA certified farms had less insect diversity compared to non-RA certified farms and that both farm types had less insect diversity than organic farms. There was little difference between RA and non-RA certified farms with regards bird community composition. Thus, organic farming conserves biodiversity, while alternative environmental labels (e.g. a Rainforest alliance seal) may not have any visible positive effect on in-farm biodiversity. This study points to the need for improvements in SAN certification standards to achieve improved environmental conditions.

    Composition of fungal soil communities varies with plant abundance and geographic origin
    Reininger, Vanessa ; Martinez-garcia, Laura B. ; Sanderson, Laura ; Antunes, Pedro M. - \ 2015
    AoB Plants 7 (2015). - ISSN 2041-2851
    Interactions of belowground fungal communities with exotic and native plant species may be important drivers of plant community structure in invaded grasslands. However, field surveys linking plant community structure with belowground fungal communities are missing. We investigated whether a selected number of abundant and relatively rare plants, either native or exotic, from an old-field site associate with different fungal communities. We also assessed whether these plants showed different symbiotic relationships with soil biota through their roots. We characterized the plant community and collected roots to investigate fungal communities using 454 pyrosequencing and assessed arbuscular mycorrhizal colonization and enemy-induced lesions. Differences in fungal communities were considered based on the assessment of α- and β diversity depending on plant ‘abundance’ and ‘origin’. Plant abundance and origin determined the fungal community. Fungal richness was higher for native abundant as opposed to relatively rare native plant species. However, this was not observed for exotics of contrasting abundance. Regardless of their origin, β diversity was higher for rare than for abundant species. Abundant exotics in the community, which happen to be grasses, were the least mycorrhizal whereas rare natives were most susceptible to enemy attack. Our results suggest that compared with exotics, the relative abundance of remnant native plant species in our old-field site is still linked to the structure of belowground fungal communities. In contrast, exotic species may act as a disturbing agent contributing towards the homogenization of soil fungal communities, potentially changing feedback interactions.
    Legume phylogeny and classification in the 21st century: Progress, prospects and lessons for other species-rich clades
    Bruneau, A. ; Doyle, J.J. ; Herendeen, P. ; Hughes, C. ; Kenicer, G. ; Lewis, G. ; Mackinder, B.A. ; Pennington, R.T. ; Sanderson, M.J. ; Wojciechowski, M.F. ; Boatwright, S. ; Brown, G. ; Cardoso, D. ; Crips, M. ; Egan, A. ; Fortunato, R. ; Hawkins, J. ; Kajita, T. ; Klitgaard, B.B. ; Koenen, E. ; Lavin, M. ; Luckow, M. ; Marazzi, B. ; McMahon, M.M. ; Miller, J.T. ; Murphy, D.J. ; Ohashi, H. ; Queiroz, L.P. de; Rico, L. ; Särkinen, T. ; Schrire, B. ; Simon, M.F. ; Souza, E.R. ; Steele, K. ; Torke, B.M. ; Wieringa, J.J. ; Wijk, B.E. - \ 2013
    Taxon 62 (2013)2. - ISSN 0040-0262 - p. 217 - 248.
    swartzia leguminosae-papilionoideae - tribe millettieae leguminosae - chloroplast dna regions - southern south-america - intron spacer regions - matk coding sequence - plastid trnl-f - molecular phylogenetics - divergence times - s.l. leguminosae
    The Leguminosae, the third-largest angiosperm family, has a global distribution and high ecological and economic importance. We examine how the legume systematic research community might join forces to produce a comprehensive phylogenetic estimate for the ca. 751 genera and ca. 19,500 species of legumes and then translate it into a phylogeny-based classification. We review the current state of knowledge of legume phylogeny and highlight where problems lie, for example in taxon sampling and phylogenetic resolution. We review approaches from bioinformatics and next-generation sequencing, which can facilitate the production of better phylogenetic estimates. Finally, we examine how morphology can be incorporated into legume phylogeny to address issues in comparative biology and classification. Our goal is to stimulate the research needed to improve our knowledge of legume phylogeny and evolution; the approaches that we discuss may also be relevant to other species-rich angiosperm clades
    Research Agenda and Policy Input of the Earth System Science Partnership for Coping with Global Environmental Change
    Leemans, R. ; Rice, M. ; Henderson-Sellers, A. ; Noone, K. - \ 2011
    In: Coping with Global Environmental Change, Disasters and Security: Threats, Challenges, Vulnerabilities and Risks / Brauch, H.G., Oswald Spring, U., Mesjasz, C., Grin, J., Kameri-Mbote, P., Chourou, B., Dunay, P., Birkmann, J., Berlijn : Springer (Hexagon Series on Human and Environmental Secutiry and Peace 5) - ISBN 9783642177750 - p. 1205 - 1220.
    Human activities now match (and often exceed) the natural forces of the Earth System (Steffen/Sanderson/ Tyson/Jäger/Matson/Moore/Oldfield/Richardson/ Schellnhuber/Turner/Wasson 2004). Recent ice core data show that current levels of carbon dioxide (CO2) and methane are well outside the range of natural variability over the last 800,000 years (Luthi/Le Floch/ Bereiter/Blunier/Barnola/Siegenthaler/Raynaud/Jouzel/ Fischer/Kawamura/Stocker 2008). Roughly half of the world’s ice-free land surface has been altered by human actions. Humans now fix more nitrogen than does nature. Particles emitted by human activities alter the energy balance of the planet, as well as having adverse effects on human health. Human choices about how we use resources are at the heart of many of these changes. These may seem to be unrelated issues; however, over the last decades, we have gained a deeper understanding of the degree to which all of these separate issues are linked. The Earth System is a very complex coupled system with myriad feedbacks, and it has and inevitably can still exhibit rapid, globalscale responses to changes in environmental conditions (Costanza/Graumlich/Steffen/Crumley/Dearing/Hibbard/ Leemans/Redman/Schimel 2007).
    PPARs: important regulators in metabolism and inflammation
    Sanderson, L. ; Kersten, A.H. - \ 2010
    In: Nuclear Receptors : current concepts and future challenges / Bunce, C.M., Campbell, M.J., Dordrecht : Springer-Verlag (Proteins and cell regulation 8) - ISBN 9789048133024 - p. 259 - 285.
    The ligand-activated family of peroxisome proliferator activated receptors (PPARs) consists of three members named PPARα, PPARδ and PPARγ. Each PPAR subtype is characterized by a specific tissue expression pattern, partially accounting for distinct biological functions. Analogous to many other nuclear receptors, PPARs form heterodimers with the retinoid X receptor and regulate DNA transcription by binding to specific response elements present in target genes.

    PPARα (NR1C1) is highly expressed in liver, heart, intestine, skeletal muscle, and various immune cells. Agonists for PPARα include the lipid-lowering fibrate drugs as well as numerous fatty acids and eicosanoids. PPARα is known to play an important role in many different metabolic processes, especially under conditions of fasting, and has proven to be an important regulator of inflammation via inhibition of gene expression.

    PPARδ (NR1C2) is ubiquitously expressed but its function has mainly been studied in skin, heart, and skeletal muscle. In the past few years, it has become evident that PPARδ is involved in numerous biological processes including lipid metabolism, wound healing and inflammation.

    The most studied PPAR subtype is PPARγ (NR1C3), which is expressed at high levels in adipose tissue, macrophages and vascular cells. PPARγ drives adipocyte differentiation, has important regulatory roles during fat storage and glucose metabolism, and is an important suppressor of inflammation. Importantly, it serves as the molecular target for the thiazolidionedione drugs.

    In this chapter we provide an overview of the major functions of the three PPAR subtypes, and focus on their role in metabolic and inflammatory processes.
    Spatial distribution of livestock concentration areas and soil nutrients in pastures
    Sanderson, M.A. ; Schmidt, J. ; Feldmand, C. ; Herrmann, A. - \ 2010
    Journal of Soil and Water Conservation 65 (2010)3. - ISSN 0022-4561 - p. 180 - 189.
    tall fescue - potassium distribution - phosphorus runoff - grazed pastures - cattle - grasslands - management - fertilization - landscape - patterns
    Livestock concentration areas can be significant point sources of nutrient pollution. Our objective was to determine the spatial distribution of livestock concentration areas in pastures at the farm scale, along with the distribution of soil nutrients at the individual livestock concentration area scale. We georeferenced and measured the size of all livestock concentration areas in cool-season grass-legume pastures on five farms (four grazing dairies and a beef cattle farm) in Maryland, Pennsylvania, and New York during two years. Soil of selected concentration areas on each of the farms was sampled to 0 to 5 and 0 to 15 cm (0 to 2 and 0 to 6 in) depths to compare nutrient levels with paired unaffected areas of the pasture. On one farm, we sampled two concentration areas more densely (20 to 25 samples, 0 to 5 cm depth along each of five 100 m [328 ft] transects) to measure spatial distribution of soil nutrients. The transects were arranged radially to encompass variation both up and downslope. We installed runoff plots at three locations on and near the two concentration areas to measure nutrients in surface water runoff from simulated rainfall. On the five farms, concentration areas occurred most frequently at paddock gates (38% of sites). Although fewer in number, concentration areas at feeding sites were often larger than those at gates or other locations and accounted for most (48%) of the area affected by livestock congregation. Most concentration areas were small (median area 100 m2 [1,076 ft2]), isolated (median distance, 61 m [200 ft] from a water body), and surrounded by vegetation. Intensive sampling on one farm showed that soil within 20 to 40 m (66 to 132 ft) of concentration areas was enriched in phosphorus, which contributed to higher phosphorus concentration in the runoff from simulated rainfall compared with the rest of the pasture. Pastures used as holding and feeding areas with highly elevated soil nutrients and no surrounding vegetation to filter runoff represented a direct threat to surface water quality. Many concentration areas, however, were surrounded by vegetation, which would mitigate this risk
    Regression procedures for relationships between random variables
    Dhanoa, M.S. ; Sanderson, R. ; Lopez, S. ; Dijkstra, J. ; Kebreab, E. ; France, J. - \ 2010
    In: Modelling Nutrient Digestion and Utilisation in Farm Animals / Sauvant, D., van Milgen, J., Faverdin, P., Friggens, N., Wageningen : Wageningen Academic Publishers - ISBN 9789086861569 - p. 31 - 39.
    Estimating maintenance energy using type I and type II regression models.
    Dhanoa, M.S. ; Sanderson, R. ; Lopez, S. ; Dijkstra, J. ; Kebreab, E. ; France, J. - \ 2010
    In: 3rd EAAP International Symposium on Energy and Protein Metabolism and Nutrition, Parma, Italy, 6 - 10 September, 2010. - Wageningen : Wageningen Academic Publishers - ISBN 9789086861538 - p. 559 - 560.
    Transcriptional profiling reveals divergent roles of PPARa and PPARß/d in regulation of gene expression in mouse liver
    Sanderson, L. ; Boekschoten, M.V. ; Desvergne, B. ; Müller, M.R. ; Kersten, A.H. - \ 2010
    Physiological genomics 41 (2010)1. - ISSN 1094-8341 - p. 42 - 52.
    activated receptor-beta/delta - nuclear hormone-receptors - acid transport protein - hepatic stellate cells - skeletal-muscle cells - lipid-metabolism - fat-metabolism - kupffer cells - delta agonist - beta
    Little is known about the role of the transcription factor peroxisome proliferator-activated receptor (PPAR) ß/ in liver. Here we set out to better elucidate the function of PPARß/ in liver by comparing the effect of PPAR and PPARß/ deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPAR and PPARß/ deletion was similar, whereas in fasted state the effect of PPAR deletion was much more pronounced, consistent with the pattern of gene expression of PPAR and PPARß/. Minor overlap was found between PPAR- and PPARß/-dependent gene regulation in liver. Pathways upregulated by PPARß/ deletion were connected to innate immunity and inflammation. Pathways downregulated by PPARß/ deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARß/–/– mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARß/ target genes. In contrast to PPAR–/– mice, no changes in plasma free fatty acid, plasma ß-hydroxybutyrate, liver triglycerides, and liver glycogen were observed in PPARß/–/– mice. Our data indicate that PPARß/ governs glucose utilization and lipoprotein metabolism and has an important anti-inflammatory role in liver. Overall, our analysis reveals divergent roles of PPAR and PPARß/ in regulation of gene expression in mouse liver
    mRNA profiling reveals divergent roles of PPARa and PPARß/d in regulating mouse liver gene expression (PPARa samples)
    Sanderson-Kjellberg, L.M. ; Boekschoten, Mark ; Desvergne, Beatrice ; Muller, Michael ; Kersten, Sander - \ 2009
    Wageningen University
    Mus musculus - GSE17863 - PRJNA123549 - Mus musculus - GSE17863
    Little is known about the role of the transcription factor PPARß/d in liver. Here we set out to better elucidate the function of PPARß/d in liver by comparing the effect of PPARa and PPARß/d deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARa and PPARß/d deletion was similar, whereas in fasted state the effect of PPARa deletion was much more pronounced, consistent with the pattern of gene expression of PPARa and PPARß/d. Minor overlap was found between PPARa- and PPARß/d-dependent gene regulation in liver. Pathways upregulated by PPARß/d deletion were connected to innate immunity. Pathways downregulated by PPARß/d deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARß/d-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARß/d target genes. In contrast to PPARa-/- mice, no changes in plasma FFA, plasma ß-hydroxybutyrate, liver triglycerides and liver glycogen were observed in PPARß/d-/- mice. Our data indicate a role for PPARß/d in hepatic glucose utilization and lipoprotein metabolism but not in the adaptive response to fasting.
    mRNA profiling reveals divergent roles of PPARa and PPARß/d in regulating mouse liver gene expression (PPARb/d samples)
    Sanderson-Kjellberg, L.M. ; Boekschoten, Mark ; Desvergne, Beatrice ; Muller, Michael ; Kersten, Sander - \ 2009
    Wageningen University
    Mus musculus - GSE17864 - PRJNA123551 - Mus musculus - GSE17864
    Little is known about the role of the transcription factor PPARß/d in liver. Here we set out to better elucidate the function of PPARß/d in liver by comparing the effect of PPARa and PPARß/d deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARa and PPARß/d deletion was similar, whereas in fasted state the effect of PPARa deletion was much more pronounced, consistent with the pattern of gene expression of PPARa and PPARß/d. Minor overlap was found between PPARa- and PPARß/d-dependent gene regulation in liver. Pathways upregulated by PPARß/d deletion were connected to innate immunity. Pathways downregulated by PPARß/d deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARß/d-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARß/d target genes. In contrast to PPARa-/- mice, no changes in plasma FFA, plasma ß-hydroxybutyrate, liver triglycerides and liver glycogen were observed in PPARß/d-/- mice. Our data indicate a role for PPARß/d in hepatic glucose utilization and lipoprotein metabolism but not in the adaptive response to fasting.
    Peroxisome Proliferator-Activated Receptor ß/ (PPARß/) but Not PPAR Serves as a Plasma Free Fatty Acid Sensor in Liver
    Sanderson, L. ; Degerhardt, T. ; Desvergne, B. ; Koppen, A. ; Kalkhoven, E. ; Müller, M.R. ; Kersten, A.H. - \ 2009
    Molecular and Cellular Biology 29 (2009)23. - ISSN 0270-7306 - p. 6257 - 6267.
    element-binding protein-1 - hepatic lipid-metabolism - gene-expression - target genes - transcription factor - hypolipidemic drugs - coactivator pgc-1 - fasting response - lipogenic genes - gamma
    Peroxisome proliferator-activated receptor alpha (PPAR alpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPAR alpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPAR alpha, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPAR beta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPAR alpha. Binding of PPAR beta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPAR beta/delta by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPAR beta/delta. In contrast, the data did not support activation of PPAR alpha by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPAR beta/delta target genes and show that upregulation of gene expression by PPAR beta/delta is sensitive to plasma FFA levels. In contrast, this is not the case for PPAR alpha, revealing a novel mechanism for functional differentiation between PPARs.
    Exploring the activation and function of PPARa and PPARß/d using genomics
    Sanderson-Kjellberg, L.M. - \ 2009
    Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Sander Kersten. - [S.l. : S.n. - ISBN 9789085854555 - 200
    lipidenmetabolisme - lever - vetzuren - genexpressie - nutrigenomica - lipid metabolism - liver - fatty acids - gene expression - nutrigenomics
    For many tissues fatty acids represent the major source of fuel. In the past few decades it has become evident that in addition to their role as energy substrates, fatty acids also have an important signaling function by modulating transcription of genes. An important group of transcription factors involved in mediating the effects of dietary fatty acids on gene transcription are the Peroxisome Proliferator-Activated Receptors (PPARs). PPARs are members of the superfamily of nuclear hormone receptors and regulate genes involved in numerous important biological processes, ranging from lipid metabolism to inflammation and wound healing. In the liver the dominant PPAR isoform has been show to be PPARα, although PPARβ/δ and PPARγ are expressed in liver as well.

    The aim of this thesis was to further characterize the role of PPARα and PPARβ/δ in hepatic metabolism and study their activation by fatty acids. Even though PPARα as gene regulator in liver has been well described, a complete overview of its target genes has been lacking so far. By combining several nutrigenomics tools, we succeeded in creating a comprehensive list of PPARα-regulated genes involved in lipid metabolism in liver. Additionally, by using a unique design where mice were fed synthetic triglycerides consisting of one type of fatty acid, we could distinguish between different types of dietary unsaturated fatty acids in their ability to activate PPARα. Although it is well known that PPARα plays an important role in liver during fasting, no direct in vivo evidence exists that circulating free fatty acids are able to ligand activate hepatic PPARα. In our studies, we found that upregulation of gene expression by PPARβ/δ is sensitive to circulating plasma free fatty acids whereas this is not the case for PPARα. Not much is known about the function of PPARβ/δ in the liver. In order to better understand the role of this nuclear receptor, we compared the effects of PPARα and PPARβ/δ deletion on whole genome gene regulation and plasma and liver metabolites. Our results revealed that PPARβ/δ does not mediate an adaptive response to fasting, and pointed to a role for PPARβ/δ in hepatic glucose- and lipoprotein metabolism.

    In conclusion, this thesis contributes to the important work of mapping the molecular mechanisms dictating lipid metabolism in the liver. By using several nutrigenomics tools, we are able to show that PPARα is a key mediator of the effect of dietary fatty acids on hepatic gene expression. In addition, we better define the roles of PPARα and PPARβ/δ in hepatic metabolism and provide a new concept for functional differentiation between PPARs in liver.

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