Obesity induced by a pair-fed high fat sucrose diet: methylation and expression pattern of genes related to energy homeostasis.

BACKGROUND: The expression of some genes controlling energy homeostasis could be regulated by epigenetic mechanisms that may play a role in body weight regulation. Thus, it is known that various nutritional factors affect DNA methylation. In order to assess whether the macronutrient composition of the diet could be related to the epigenetic regulation of gene expression and with obesity development, we investigated the effects on methylation and expression patterns of two pair-fed isocaloric diets in rats: control (rich in starch) and HFS (rich in fat and sucrose). RESULTS: The pair-fed HFS diet induced higher weight gain and adiposity as compared to the controls as well as liver triglyceride accumulation and oxidative stress. Feeding the HFS diet impaired glucose tolerance and serum triglycerides and cholesterol. Liver glucokinase expression, a key glycolytic gene, remained unaltered, as well as the mRNA values of fatty acid synthase and NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6 (NDUFB6) in liver and visceral adipocytes, which regulate lipogenesis and mitochondrial oxidative metabolism, respectively. Liver expression of hydroxyacyl-coenzyme A dehydrogenase (HADHB), a key gene of beta-oxidation pathway, was higher in the HFS-fed animals. However, the methylation status of CpG islands in HADHB and glucokinase genes remained unchanged after feeding the HFS diet. CONCLUSIONS: These results confirm that the distribution and type of macronutrients (starch vs. sucrose, and percent of fat) influence obesity onset and the associated metabolic complications. HFS diets produce obesity independently of total energy intake, although apparently no epigenetic (DNA methylation) changes accompanied the modifications observed in gene expression

Deliverable D2:Consolidation of needs of the european wasten management agencies and the regulator of the consortium: Work Package 1, Site-specific and palaeo environmental data. Modelling sequential biosphere systems under climate change for radioactive waste disposal. (BIOCLIM)

The nature of long-lived radioactive wastes is that they present a radiological hazard over a period of time that is extremely long compared with the timescale over which the engineered protection systems and institutional management of a disposal, or long-term storage, facility can be guaranteed. Safety assessments for potential deep repositories need to be able to provide indicators of safety performance over time periods of hundreds of thousands of years. On such timescales, it is generally assumed that radionuclides may be slowly released from the containment system, migrating via geosphere pathways until they reach the accessible environment. Hence, there is a need to study the evolution of the environment external to the disposal system and the ways in which this might impact on its long-term radiological safety performance, for example in terms of influences on the migration and accumulation of radionuclides

Deliverable D3: Global climatic features over the next million years and recommendation for specific situations to be considered. Work Package 2, Simulation of the future evolution of the biosphere system using the hierarchical strategy. Modelling Sequential Biosphere Systems under Climate Change for Radioactive Waste Disposal (BIOCLIM)

The BIOCLIM project aims at assessing the possible long-term impacts of climate change on the safety of waste repositories in deep formations using climate simulations of the long-term climate in various European areas. One of the objectives of the project is to develop two strategies for representing sequential climatic changes to the geosphere-biosphere system for different sites over Europe, addressing the time scale of one million years. The results of this work will be interpreted in terms of global or regional changes of climate and of vegetation. The first strategy (hierarchical strategy) will use the full hierarchy of existing climate models (a climate model is a numerical simplified representation of the climate system behaviour and evolution). Simple models (LLN 2-D NH and threshold models; see the description here after) will simulate the overall long-term evolution of the global climate. Their results will then be used as inputs to more complex models (LMD climate models possibly coupled with vegetation models, either SECHIBA or ORCHIDE) and finally climate and vegetation cover will be determined for specific sites at specific times. A second strategy (integrated strategy) will consist in building an integrated climate model, which represents most of the physical mechanisms for studying long-term climatic variations. The results will then be interpreted on a regional scale. This deliverable is the first step of the hierarchical strategy. The purpose of this deliverable is to identify and justify some specific climatic situations amongst different long-term simulations that are of interest for assessing the safety of radioactive waste repository sites and that will be further studied with GCMs (General Circulation Model)

Deliverable D4/5: Global climatic characteristics, including vegetation and seasonal cycles over Europe, for snapshots over the next 200,000 years. Work Package 2, Simulation of the future evolution of the biosphere system using the hierarchical strategy. Modelling Sequential Biosphere Systems under Climate Change for Radioactive Waste Disposal (BIOCLIM)

The aim of the BIOCLIM project is to develop and present techniques that can be used to develop self-consistent patterns of possible future climate changes over the next million years (climate scenarios), and to demonstrate how these climate scenarios can be used in assessments of the long-term safety of nuclear waste repository sites. Within the project, two strategies are implemented to predict climate change. The first is the hierarchical strategy, in which a hierarchy of climate models is used to investigate the evolution of climate over the period of interest. These models vary from very simple 2-D and threshold models, which simulate interactions between only a few aspects of the earth system, through general circulation models (GCMs) and vegetation models, which simulate in great detail the dynamics and physics of the atmosphere, ocean, and biosphere, to regional models, which focus in particular on the European region and the specific areas of interest. The second strategy is the integrated strategy, in which intermediate complexity climate models are developed, and used to consecutively simulate the development of the earth system over many millennia. Although these models are relatively simple compared to a GCM, they are more advanced than 2D models, and do include physical descriptions of the biosphere, cryosphere, atmosphere and ocean. This deliverable, D4/5, focuses on the hierarchical strategy, and in particular the GCM and vegetation model simulation of possible future climates. Deliverable D3 documented the first step in this strategy. The Louvain-la-Neuve 2-D climate model (LLN-2D) was used to estimate (among other variables) annual mean temperatures and ice volume in the Northern Hemisphere over the next 1 million years. It was driven by the calculated evolution of orbital parameters, and plausible scenarios of CO2 concentration. From the results, 3 future time periods within the next 200,000 years were identified as being extreme, that is either significantly warmer or cooler than the present. The next stage in the hierarchical strategy was to use a GCM and biosphere model, to simulate in more detail these extreme time periods

Deliverable D6a: Regional climatic characteristics for the European sites at specific times: the dynamical downscaling. Work Package 2, Simulation of the future evolution of the biosphere system using the hierarchical strategy. Modelling Sequential Biosphere Systems under Climate Change for Radioactive Waste Disposal (BIOCLIM)

The overall aim of BIOCLIM is to assess the possible long-term impacts due to climate change on the safety of radioactive waste repositories in deep formations. This aim is addressed through the following specific objectives: • Development of practical and innovative strategies for representing sequential climatic changes to the geosphere-biosphere system for existing sites over central Europe, addressing the timescale of one million years, which is relevant to the geological disposal of radioactive waste. • Exploration and evaluation of the potential effects of climate change on the nature of the biosphere systems used to assess the environmental impact. • Dissemination of information on the new methodologies and the results obtained from the project among the international waste management community for use in performance assessments of potential or planned radioactive waste repositories. The BIOCLIM project is designed to advance the state-of-the-art of biosphere modelling for use in Performance Assessments. Therefore, two strategies are developed for representing sequential climatic changes to geosphere-biosphere systems. The hierarchical strategy successively uses a hierarchy of climate models. These models vary from simple 2-D models, which simulate interactions between a few aspects of the Earth system at a rough surface resolution, through General Circulation Model (GCM) and vegetation model, which simulate in great detail the dynamics and physics of the atmosphere, ocean and biosphere, to regional models, which focus on the European regions and sites of interest. Moreover, rule-based and statistical downscaling procedures are also considered. Comparisons are provided in terms of climate and vegetation cover at the selected times and for the study regions. The integrated strategy consists of using integrated climate models, representing all the physical mechanisms important for long-term continuous climate variations, to simulate the climate evolution over many millennia. These results are then interpreted in terms of regional climatic changes using rule-based and statistical downscaling approaches. This deliverable, D6a, focuses on the hierarchical strategy, and in particular the MAR simulations. According to the hierarchical strategy developed in the BIOCLIM project to predict future climate, six BIOCLIM experiments were run with the MAR model. In addition to these experiments a baseline experiment, presenting the present-day climate simulated by MAR, was also undertaken. In the first step of the hierarchical strategy the LLN 2-D NH climate model simulated the gross features of the climate of the next 1 Myr [Ref.1]. Six snapshot experiments were selected from these results. In a second step a GCM and a biosphere model were used to simulate in more detail the climate of the selected time periods. These simulations were performed on a global scale [Ref.1]. The third step of the procedure is to derive the regional features of the climate at the same time periods. Therefore the results of the GCM are used as boundary conditions to force the regional climate model (MAR) for the six selected periods and the baseline simulation. The control simulation (baseline) corresponds to the regional climate simulated under present-day conditions, both insolation forcing and atmospheric CO2 concentration. All the BIOCLIM simulations are compared to that baseline simulation. In addition, other comparisons will also be presented. Tableau 1 summarises the characteristics of these BIOCLIM experiments already presented in [Ref.1] and [Ref.2]

Deliverable D8a: Development of the rule-based downscaling methodology for BIOCLIM Workpackage 3. Work Package 3, Simulation of the future evolution of the biosphere system using the hierarchical strategy. Modelling Sequential Biosphere Systems under Climate Change for Radioactive Waste Disposal (BIOCLIM)

One of the tasks of BIOCLIM WP3 was to develop a rule-based approach for downscaling from the MoBidiC model of intermediate complexity (see Ref.1) in order to provide consistent estimates of monthly temperature and precipitation for the specific regions of interest to BIOCLIM (Central Spain, Central England and Northeast France, together with Germany and the Czech Republic). Such an approach has been developed and used in a previous study funded by Nirex to downscale output from an earlier version of this climate model covering the Northern Hemisphere only, LLN 2-D NH, to Central England, and evaluated using palaeoclimate proxy data and General Circulation Model (GCM) output for this region. This previous study [Ref.2] provides the starting point for the BIOCLIM work. A statistical downscaling methodology has been developed by Philippe Marbaix of CEA/LSCE for use with the second climate model of intermediate complexity used in BIOCLIM – CLIMBER-GREMLINS (see Ref.1). This statistical methodology is described in Deliverable D8b [Ref.3]. Inter-comparisons of all the downscaling methodologies used in BIOCLIM (including the dynamical methods applied in WP2 – see Ref.4 and Ref.5) are discussed in Deliverable D10-12 [Ref.6]. The rule-based methodology assigns climate states or classes to a point on the time continuum of a region according to a combination of simple threshold values which can be determined from the coarse scale climate model. Once climate states or classes have been defined, monthly temperature and precipitation climatologies are constructed using analogue stations identified from a data base of present-day climate observations. The most appropriate climate classification for BIOCLIM purposes is the Køppen/Trewartha scheme (Ref.7 ; see Appendix 1). This scheme has the advantage of being empirical, but only requires monthly averages of temperature and precipitation as input variables

Deliverable D7: Continuous climate evolution scenarios over western Europe (1000 km) scale. Work Package 2, Simulation of the future evolution of the biosphere system using the hierarchical strategy. Modelling Sequential Biosphere Systems under Climate Change for Radioactive Waste Disposal (BIOCLIM)

The overall aim of BIOCLIM is to assess the possible long term impacts due to climate change on the safety of radioactive waste repositories in deep formations. This aim is addressed through the following specific objectives: • Development of practical and innovative strategies for representing sequential climatic changes to the geosphere-biosphere system for existing sites over central Europe, addressing the timescale of one million years, which is relevant to the geological disposal of radioactive waste. • Exploration and evaluation of the potential effects of climate change on the nature of the biosphere systems used to assess the environmental impact. • Dissemination of information on the new methodologies and the results obtained from the project among the international waste management community for use in performance assessments of potential or planned radioactive waste repositories. A key point of the project is therefore to develop strategies for representing sequential long-term climatic changes by addressing time scales of relevance to geological disposal of solid radioactive wastes. The integrated strategy, which first step is described in this deliverable (D7), consists of building an integrated, dynamic climate model, to represent all the known important mechanisms for long term climatic variations. The time-dependent results will then be interpreted in terms of regional climate using rulebased and statistical downscaling approaches. Therefore, the continuous simulation of the climate evolution of the next 200 000 years selected for study is a major objective of the BIOCLIM project. This requires models that account for the simultaneous evolution of the atmosphere, biosphere, land-ice and the ocean. To be able to perform several 200 000-yearlong transient climate simulations, the models have to include all these components, but also need to be simple enough to run fast. Therefore, climate models of intermediate complexity have been chosen to complete this part of the BIOCLIM project. In the present deliverable, we report on the results of two such models, MoBidiC (Louvain-la-Neuve) and CLIMBER-GREMLINS (LSCE). The overall objective of the work presented here is the simulation of the climate of the next 200 000 years for three different CO2 scenarios [Ref.1]. However, both models used for this work have been either modified for the project (MoBidiC) or developed within the project (CLIMBERGREMLINS). Therefore their performance, and the modifications and developments needed to be documented, especially as far as their ability to reproduce past and different climates is concerned. Therefore, a large section of the present deliverable is devoted to the evaluation of the models through past climate simulations. The deliverable is structured as follows: first, a brief description of the models is given. In the second section, results from the models for past climate situations are presented. The third section deals with the future climate simulations devised for the BIOCLIM project: for each CO2 scenario, the results of the two models are compared. It is emphasized that the model results, especially those for CLIMBER-GREMLINS, should be regarded as illustrations of possibilities rather than absolute predictions of climate evolution. The novel approach to long-term climate change adopted in BIOCLIM is based on research tools under continuing development, notably, the CLIMBER-GREMLINS model

Deliverable D10/12: Development and application of a methology for taking climate-driven environmental change into account in performance assessments.Work package 4:Biosphere System Description. Modelling Sequential Biosphere Systems under Climate Change for Radioactive Waste Disposal(BIOCLIM)

The aim of the BIOCLIM project has been to provide a scientific basis and practical methodology for assessing the potential impacts of long-term climate change on biosphere characteristics in the context of radiological performance assessments (PA) of radioactive waste repositories in deep geological formations. The project brought together twelve different European organisations plus associated sub-contractors with responsibilities for either the safe disposal of radioactive waste or the development of climate models. Through this scientific and technical collaboration, climate models that can simulate future climate changes in Europe over very long timescales have been developed. The climate modelling results have been linked to an understanding of the pattern of biosphere changes for selected European regions in order to address the issue of how to represent future biosphere systems in long term radiological performance assessments. The project was implemented through five work packages (WP)

Deliverable D8b: Development of the physical/statistical downscaling methodology and application to climate model CLIMBER for BIOCLIM Workpackage 3. Work Package 3, Simulation of the future evolution of the biosphere system using the hierarchical strategy. Modelling Sequential Biosphere Systems under Climate Change for Radioactive Waste Disposal (BIOCLIM)

The overall aim of BIOCLIM is to assess the possible long term impacts due to climate change on the safety of radioactive waste repositories in deep formations. This aim is addressed through the following specific objectives: • Development of practical and innovative strategies for representing sequential climatic changes to the geosphere-biosphere system for existing sites over central Europe, addressing the timescale of one million years, which is relevant to the geological disposal of radioactive waste. • Exploration and evaluation of the potential effects of climate change on the nature of the biosphere systems used to assess the environmental impact. • Dissemination of information on the new methodologies and the results obtained from the project among the international waste management community for use in performance assessments of potential or planned radioactive waste repositories. This deliverable has the following specific motivations and objectives: Its main aim is to provide time series of climatic variables at the high resolution as needed by performance assessment (PA) of radioactive waste repositories, on the basis of coarse output from the CLIMBER-GREMLINS climate model