| 1. |
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| 2. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 3. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 4. |
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| 5. |
- Janssen, Annette B. G., et al.
(författare)
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Exploring, exploiting and evolving diversity of aquatic ecosystem models : a community perspective
- 2015
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Ingår i: Aquatic Ecology. - : Springer Science and Business Media LLC. - 1386-2588 .- 1573-5125. ; 49:4, s. 513-548
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Tidskriftsartikel (refereegranskat)abstract
- Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity by comparing and combining different aspects of existing models. Finally, we discuss how model diversity came about in the past and could evolve in the future. Throughout our study, we use analogies from biodiversity research to analyse and interpret model diversity. We recommend to make models publicly available through open-source policies, to standardize documentation and technical implementation of models, and to compare models through ensemble modelling and interdisciplinary approaches. We end with our perspective on how the field of aquatic ecosystem modelling might develop in the next 5-10 years. To strive for clarity and to improve readability for non-modellers, we include a glossary.
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| 6. |
- Bowers, Robert M., et al.
(författare)
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Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea
- 2017
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Ingår i: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 35:8, s. 725-731
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Tidskriftsartikel (refereegranskat)abstract
- We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a Metagenome-Assembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Gene Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.
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| 7. |
- Akperov, M., et al.
(författare)
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Trends of intense cyclone activity in the Arctic from reanalyses data and regional climate models (Arctic-CORDEX)
- 2019. - 1
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Ingår i: Turbulence, Atmosphere and Climate Dynamics. - : IOP Publishing. - 1755-1307. ; 231
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Konferensbidrag (refereegranskat)abstract
- The ability of state-of-the-art regional climate models (RCMs) to simulate the trends of intense cyclone activity in the Arctic is assessed based on an ensemble of 13 simulations from 11 models from the Arctic-CORDEX initiative. Some models employ large-scale spectral nudging techniques. Cyclone characteristics simulated by the ensemble in winter and summer are compared with the results from four reanalyses (ERA-Interim, NCEP-CFSR, NASA-MERRA2 and JMA-JRA55) in winter and summer for 1981-2010 period.
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| 8. |
- Bruce, Louise C, et al.
(författare)
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A multi-lake comparative analysis of the General Lake Model (GLM) : Stress-testing across a global observatory network
- 2018
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Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152 .- 1873-6726. ; 102, s. 274-291
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Tidskriftsartikel (refereegranskat)abstract
- The modelling community has identified challenges for the integration and assessment of lake models due to the diversity of modelling approaches and lakes. In this study, we develop and assess a one-dimensional lake model and apply it to 32 lakes from a global observatory network. The data set included lakes over broad ranges in latitude, climatic zones, size, residence time, mixing regime and trophic level. Model performance was evaluated using several error assessment metrics, and a sensitivity analysis was conducted for nine parameters that governed the surface heat exchange and mixing efficiency. There was low correlation between input data uncertainty and model performance and predictions of temperature were less sensitive to model parameters than prediction of thermocline depth and Schmidt stability. The study provides guidance to where the general model approach and associated assumptions work, and cases where adjustments to model parameterisations and/or structure are required.
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| 9. |
- McGuire, A. David, et al.
(författare)
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Variability in the sensitivity among model simulations of permafrost and carbon dynamics in the permafrost region between 1960 and 2009
- 2016
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 30:7, s. 1015-1037
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Tidskriftsartikel (refereegranskat)abstract
- A significant portion of the large amount of carbon (C) currently stored in soils of the permafrost region in the Northern Hemisphere has the potential to be emitted as the greenhouse gases CO2 and CH4 under a warmer climate. In this study we evaluated the variability in the sensitivity of permafrost and C in recent decades among land surface model simulations over the permafrost region between 1960 and 2009. The 15 model simulations all predict a loss of near-surface permafrost (within 3m) area over the region, but there are large differences in the magnitude of the simulated rates of loss among the models (0.2 to 58.8x10(3)km(2)yr(-1)). Sensitivity simulations indicated that changes in air temperature largely explained changes in permafrost area, although interactions among changes in other environmental variables also played a role. All of the models indicate that both vegetation and soil C storage together have increased by 156 to 954TgCyr(-1) between 1960 and 2009 over the permafrost region even though model analyses indicate that warming alone would decrease soil C storage. Increases in gross primary production (GPP) largely explain the simulated increases in vegetation and soil C. The sensitivity of GPP to increases in atmospheric CO2 was the dominant cause of increases in GPP across the models, but comparison of simulated GPP trends across the 1982-2009 period with that of a global GPP data set indicates that all of the models overestimate the trend in GPP. Disturbance also appears to be an important factor affecting C storage, as models that consider disturbance had lower increases in C storage than models that did not consider disturbance. To improve the modeling of C in the permafrost region, there is the need for the modeling community to standardize structural representation of permafrost and carbon dynamics among models that are used to evaluate the permafrost C feedback and for the modeling and observational communities to jointly develop data sets and methodologies to more effectively benchmark models.
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| 10. |
- Peng, S., et al.
(författare)
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Simulated high-latitude soil thermal dynamics during the past 4 decades
- 2016
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0424. ; 10:1, s. 179-192
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Tidskriftsartikel (refereegranskat)abstract
- Soil temperature (Ts) change is a key indicator of the dynamics of permafrost. On seasonal and interannual timescales, the variability of Ts determines the active-layer depth, which regulates hydrological soil properties and biogeochemical processes. On the multi-decadal scale, increasing Ts not only drives permafrost thaw/retreat but can also trigger and accelerate the decomposition of soil organic carbon. The magnitude of permafrost carbon feedbacks is thus closely linked to the rate of change of soil thermal regimes. In this study, we used nine process-based ecosystem models with permafrost processes, all forced by different observation-based climate forcing during the period 1960–2000, to characterize the warming rate of Ts in permafrost regions. There is a large spread of Ts trends at 20 cm depth across the models, with trend values ranging from 0.010 ± 0.003 to 0.031 ± 0.005 °C yr−1. Most models show smaller increase in Ts with increasing depth. Air temperature (Tsub>a) and longwave downward radiation (LWDR) are the main drivers of Ts trends, but their relative contributions differ amongst the models. Different trends of LWDR used in the forcing of models can explain 61 % of their differences in Ts trends, while trends of Ta only explain 5 % of the differences in Ts trends. Uncertain climate forcing contributes a larger uncertainty in Ts trends (0.021 ± 0.008 °C yr−1, mean ± standard deviation) than the uncertainty of model structure (0.012 ± 0.001 °C yr−1), diagnosed from the range of response between different models, normalized to the same forcing. In addition, the loss rate of near-surface permafrost area, defined as total area where the maximum seasonal active-layer thickness (ALT) is less than 3 m loss rate, is found to be significantly correlated with the magnitude of the trends of Ts at 1 m depth across the models (R = −0.85, P = 0.003), but not with the initial total near-surface permafrost area (R = −0.30, P = 0.438). The sensitivity of the total boreal near-surface permafrost area to Ts at 1 m is estimated to be of −2.80 ± 0.67 million km2 °C−1. Finally, by using two long-term LWDR data sets and relationships between trends of LWDR and Ts across models, we infer an observation-constrained total boreal near-surface permafrost area decrease comprising between 39 ± 14 × 103 and 75 ± 14 × 103 km2 yr−1 from 1960 to 2000. This corresponds to 9–18 % degradation of the current permafrost area.
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| 11. |
- Wang, W., et al.
(författare)
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Diagnostic and model dependent uncertainty of simulated Tibetan permafrost area
- 2016
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Ingår i: Cryosphere. - : Copernicus GmbH. - 1994-0416. ; 10:1, s. 287-306
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Tidskriftsartikel (refereegranskat)abstract
- We perform a land-surface model intercomparison to investigate how the simulation of permafrost area on the Tibetan Plateau (TP) varies among six modern stand-alone land-surface models (CLM4.5, CoLM, ISBA, JULES, LPJ-GUESS, UVic). We also examine the variability in simulated permafrost area and distribution introduced by five different methods of diagnosing permafrost (from modeled monthly ground temperature, mean annual ground and air temperatures, air and surface frost indexes). There is good agreement (99 to 135 × 104km2) between the two diagnostic methods based on air temperature which are also consistent with the observation-based estimate of actual permafrost area (101 ×104km2). However the uncertainty (1 to 128 × 104km2) using the three methods that require simulation of ground temperature is much greater. Moreover simulated permafrost distribution on the TP is generally only fair to poor for these three methods (diagnosis of permafrost from monthly, and mean annual ground temperature, and surface frost index), while permafrost distribution using air-temperature-based methods is generally good. Model evaluation at field sites highlights specific problems in process simulations likely related to soil texture specification, vegetation types and snow cover. Models are particularly poor at simulating permafrost distribution using the definition that soil temperature remains at or below 0°C for 24 consecutive months, which requires reliable simulation of both mean annual ground temperatures and seasonal cycle, and hence is relatively demanding. Although models can produce better permafrost maps using mean annual ground temperature and surface frost index, analysis of simulated soil temperature profiles reveals substantial biases. The current generation of land-surface models need to reduce biases in simulated soil temperature profiles before reliable contemporary permafrost maps and predictions of changes in future permafrost distribution can be made for the Tibetan Plateau.
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| 12. |
- Akperov, Mirseid, et al.
(författare)
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Cyclone Activity in the Arctic From an Ensemble of Regional Climate Models (Arctic CORDEX)
- 2018
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Ingår i: Journal of Geophysical Research: Atmospheres. - 2169-8996 .- 2169-897X. ; 123:5, s. 2537-2554
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Tidskriftsartikel (refereegranskat)abstract
- The ability of state-of-the-art regional climate models to simulate cyclone activity in the Arctic is assessed based on an ensemble of 13 simulations from 11 models from the Arctic-CORDEX initiative. Some models employ large-scale spectral nudging techniques. Cyclone characteristics simulated by the ensemble are compared with the results forced by four reanalyses (ERA-Interim, National Centers for Environmental Prediction-Climate Forecast System Reanalysis, National Aeronautics and Space Administration-Modern-Era Retrospective analysis for Research and Applications Version 2, and Japan Meteorological Agency-Japanese 55-year reanalysis) in winter and summer for 1981-2010 period. In addition, we compare cyclone statistics between ERA-Interim and the Arctic System Reanalysis reanalyses for 2000-2010. Biases in cyclone frequency, intensity, and size over the Arctic are also quantified. Variations in cyclone frequency across the models are partly attributed to the differences in cyclone frequency over land. The variations across the models are largest for small and shallow cyclones for both seasons. A connection between biases in the zonal wind at 200 hPa and cyclone characteristics is found for both seasons. Most models underestimate zonal wind speed in both seasons, which likely leads to underestimation of cyclone mean depth and deep cyclone frequency in the Arctic. In general, the regional climate models are able to represent the spatial distribution of cyclone characteristics in the Arctic but models that employ large-scale spectral nudging show a better agreement with ERA-Interim reanalysis than the rest of the models. Trends also exhibit the benefits of nudging. Models with spectral nudging are able to reproduce the cyclone trends, whereas most of the nonnudged models fail to do so. However, the cyclone characteristics and trends are sensitive to the choice of nudged variables.
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| 13. |
- Akperov, Mirseid, et al.
(författare)
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Future projections of cyclone activity in the Arctic for the 21st century from regional climate models (Arctic-CORDEX)
- 2019
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Ingår i: Global and Planetary Change. - : Elsevier BV. - 0921-8181 .- 1872-6364. ; 182
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the characteristics of cyclone activity (frequency, depth and size) in the Arctic are analyzed based on simulations with state-of-the-art regional climate models (RCMs) from the Arctic-CORDEX initiative and global climate models (GCMs) from CMIP5 under the Representative Concentration Pathway (RCP) 8.5 scenario. Most of RCMs show an increase of cyclone frequency in winter (DJF) and a decrease in summer (JJA) to the end of the 21st century. However, in one half of the RCMs, cyclones become weaker and substantially smaller in winter and deeper and larger in summer. RCMs as well as GCMs show an increase of cyclone frequency over the Baffin Bay, Barents Sea, north of Greenland, Canadian Archipelago, and a decrease over the Nordic Seas, Kara and Beaufort Seas and over the sub-arctic continental regions in winter. In summer, the models simulate an increase of cyclone frequency over the Central Arctic and Greenland Sea and a decrease over the Norwegian and Kara Seas by the end of the 21st century. The decrease is also found over the high-latitude continental areas, in particular, over east Siberia and Alaska. The sensitivity of the RCMs' projections to the boundary conditions and model physics is estimated. In general, different lateral boundary conditions from the GCMs have larger effects on the simulated RCM projections than the differences in RCMs' setup and/or physics.
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| 14. |
- Marcé, Rafael, et al.
(författare)
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Automatic High Frequency Monitoring for Improved Lake and Reservoir Management
- 2016
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 50:20, s. 10780-10794
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Forskningsöversikt (refereegranskat)abstract
- Recent technological developments have increased the number of variables being monitored in lakes and reservoirs using automatic high frequency monitoring (AHFM). However, design of AHFM systems and posterior data handling and interpretation are currently being developed on a site-by-site and issue-by-issue basis with minimal standardization of protocols or knowledge sharing. As a result, many deployments become short-lived or underutilized, and many new scientific developments that are potentially useful for water management and environmental legislation remain underexplored. This Critical Review bridges scientific uses of AHFM with their applications by providing an overview of the current AHFM capabilities, together with examples of successful applications. We review the use of AHFM for maximizing the provision of ecosystem services supplied by lakes and reservoirs (consumptive and non consumptive uses, food production, and recreation), and for reporting lake status in the EU Water Framework Directive. We also highlight critical issues to enhance the application of AHFM, and suggest the establishment of appropriate networks to facilitate knowledge sharing and technological transfer between potential users. Finally, we give advice on how modern sensor technology can successfully be applied on a larger scale to the management of lakes and reservoirs and maximize the ecosystem services they provide.
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| 15. |
- Wang, Wenli, et al.
(författare)
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Evaluation of air-soil temperature relationships simulated by land surface models during winter across the permafrost region
- 2016
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Ingår i: Cryosphere. - : Copernicus GmbH. - 1994-0416. ; 10:4, s. 1721-1737
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Tidskriftsartikel (refereegranskat)abstract
- A realistic simulation of snow cover and its thermal properties are important for accurate modelling of permafrost. We analyse simulated relationships between air and near-surface (20 cm) soil temperatures in the Northern Hemisphere permafrost region during winter, with a particular focus on snow insulation effects in nine land surface models, and compare them with observations from 268 Russian stations. There are large cross-model differences in the simulated differences between near-surface soil and air temperatures (ΔT; 3 to 14 °C), in the sensitivity of soil-to-air temperature (0.13 to 0.96 °C °C-1), and in the relationship between ΔT and snow depth. The observed relationship between ΔT and snow depth can be used as a metric to evaluate the effects of each model's representation of snow insulation, hence guide improvements to the model's conceptual structure and process parameterisations. Models with better performance apply multilayer snow schemes and consider complex snow processes. Some models show poor performance in representing snow insulation due to underestimation of snow depth and/or overestimation of snow conductivity. Generally, models identified as most acceptable with respect to snow insulation simulate reasonable areas of near-surface permafrost (13.19 to 15.77 million km2). However, there is not a simple relationship between the sophistication of the snow insulation in the acceptable models and the simulated area of Northern Hemisphere near-surface permafrost, because several other factors, such as soil depth used in the models, the treatment of soil organic matter content, hydrology and vegetation cover, also affect the simulated permafrost distribution.
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| 16. |
- Xia, Jianyang, et al.
(författare)
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Terrestrial ecosystem model performance in simulating productivity and its vulnerability to climate change in the northern permafrost region
- 2017
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Ingår i: Journal of Geophysical Research - Biogeosciences. - 2169-8953. ; 122:2, s. 430-446
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Tidskriftsartikel (refereegranskat)abstract
- Realistic projection of future climate-carbon (C) cycle feedbacks requires better understanding and an improved representation of the C cycle in permafrost regions in the current generation of Earth system models. Here we evaluated 10 terrestrial ecosystem models for their estimates of net primary productivity (NPP) and responses to historical climate change in permafrost regions in the Northern Hemisphere. In comparison with the satellite estimate from the Moderate Resolution Imaging Spectroradiometer (MODIS; 246±6gCm-2yr-1), most models produced higher NPP (309±12gCm-2yr-1) over the permafrost region during 2000-2009. By comparing the simulated gross primary productivity (GPP) with a flux tower-based database, we found that although mean GPP among the models was only overestimated by 10% over 1982-2009, there was a twofold discrepancy among models (380 to 800gCm-2yr-1), which mainly resulted from differences in simulated maximum monthly GPP (GPPmax). Most models overestimated C use efficiency (CUE) as compared to observations at both regional and site levels. Further analysis shows that model variability of GPP and CUE are nonlinearly correlated to variability in specific leaf area and the maximum rate of carboxylation by the enzyme Rubisco at 25°C (Vcmax_25), respectively. The models also varied in their sensitivities of NPP, GPP, and CUE to historical changes in climate and atmospheric CO2 concentration. These results indicate that model predictive ability of the C cycle in permafrost regions can be improved by better representation of the processes controlling CUE and GPPmax as well as their sensitivity to climate change.
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| 17. |
- Carlsen, Esben Andreas, et al.
(författare)
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Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3 : a multicenter cohort study
- 2019
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Ingår i: Endocrine-Related Cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 26:2, s. 227-239
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Tidskriftsartikel (refereegranskat)abstract
- Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1-2 (G1-G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21-54% (n = 125) vs Ki-67 >= 55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3-4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.
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| 18. |
- Li, Zhao, et al.
(författare)
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Non-uniform seasonal warming regulates vegetation greening and atmospheric CO2 amplification over northern lands
- 2018
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- The enhanced vegetation growth by climate warming plays a pivotal role in amplifying the seasonal cycle of atmospheric CO2 at northern lands (>50° N) since 1960s. However, the correlation between vegetation growth, temperature and seasonal amplitude of atmospheric CO2 concentration have become elusive with the slowed increasing trend of vegetation growth and weakened temperature control on CO2 uptake since late 1990s. Here, based on in situ atmospheric CO2 concentration records from the Barrow observatory site, we found a slowdown in the increasing trend of the atmospheric CO2 amplitude from 1990s to mid-2000s. This phenomenon was associated with the paused decrease in the minimum CO2 concentration ([CO2]min), which was significantly correlated with the slowdown of vegetation greening and growing-season length extension. We then showed that both the vegetation greenness and growing-season length were positively correlated with spring but not autumn temperature over the northern lands. Furthermore, such asymmetric dependences of vegetation growth upon spring and autumn temperature cannot be captured by the state-of-art terrestrial biosphere models. These findings indicate that the responses of vegetation growth to spring and autumn warming are asymmetric, and highlight the need of improving autumn phenology in the models for predicting seasonal cycle of atmospheric CO2 concentration.
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| 19. |
- Oteng, Antwi-Boasiako, et al.
(författare)
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Characterization of ANGPTL4 function in macrophages and adipocytes using Angptl4-knockout and Angptl4-hypomorphic mice[S]
- 2019
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Ingår i: Journal of Lipid Research. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 0022-2275 .- 1539-7262. ; 60:10, s. 1741-1754
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Tidskriftsartikel (refereegranskat)abstract
- Angiopoietin-like protein (ANGPTL)4 regulates plasma lipids, making it an attractive target for correcting dyslipidemia. However, ANGPTL4 inactivation in mice fed a high fat diet causes chylous ascites, an acute-phase response, and mesenteric lymphadenopathy. Here, we studied the role of ANGPTL4 in lipid uptake in macrophages and in the above-mentioned pathologies using Angptl4-hypomorphic and Angptl4(-/-) mice. Angptl4 expression in peritoneal and bone marrow-derived macrophages was highly induced by lipids. Recombinant ANGPTL4 decreased lipid uptake in macrophages, whereas deficiency of ANGPTL4 increased lipid uptake, upregulated lipid-induced genes, and increased respiration. ANGPTL4 deficiency did not alter LPL protein levels in macrophages. Angptl4-hypomorphic mice with partial expression of a truncated N-terminal ANGPTL4 exhibited reduced fasting plasma triglyceride, cholesterol, and NEFAs, strongly resembling Angptl4(-/-) mice. However, during high fat feeding, Angptl4-hypomorphic mice showed markedly delayed and attenuated elevation in plasma serum amyloid A and much milder chylous ascites than Angptl4(-/-) mice, despite similar abundance of lipid-laden giant cells in mesenteric lymph nodes. In conclusion, ANGPTL4 deficiency increases lipid uptake and respiration in macrophages without affecting LPL protein levels. Compared with the absence of ANGPTL4, low levels of N-terminal ANGPTL4 mitigate the development of chylous ascites and an acute-phase response in mice.
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