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- Wang, Z., et al.
(author)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Journal article (peer-reviewed)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 5. |
- Maqdasy, S, et al.
(author)
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Impaired phosphocreatine metabolism in white adipocytes promotes inflammation
- 2022
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In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:2, s. 190-
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Journal article (peer-reviewed)abstract
- The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate white adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts and find that the WAT phosphocreatine/creatine ratio is increased and creatine kinase-B expression and activity is decreased in the obese state. In human in vitro and murine in vivo models, we demonstrate that decreased phosphocreatine metabolism in white adipocytes alters adenosine monophosphate-activated protein kinase activity via effects on adenosine triphosphate/adenosine diphosphate levels, independently of WAT beigeing. This disturbance promotes a pro-inflammatory profile characterized, in part, by increased chemokine (C-C motif) ligand 2 (CCL2) production. These data suggest that the phosphocreatine/creatine system links cellular energy shuttling with pro-inflammatory responses in human and murine white adipocytes. Our findings provide unexpected perspectives on the mechanisms driving WAT inflammation in obesity and may present avenues to target adipocyte dysfunction.
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- Reckien, D., et al.
(author)
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Dedicated versus mainstreaming approaches in local climate plans in Europe
- 2019
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In: Renewable & sustainable energy reviews. - : Elsevier. - 1364-0321 .- 1879-0690. ; 112, s. 948-959
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Journal article (peer-reviewed)abstract
- Cities are gaining prominence committing to respond to the threat of climate change, e.g., by developing local climate plans or strategies. However, little is known regarding the approaches and processes of plan development and implementation, or the success and effectiveness of proposed measures. Mainstreaming is regarded as one approach associated with (implementation) success, but the extent of integration of local climate policies and plans in ongoing sectoral and/or development planning is unclear. This paper analyses 885 cities across the 28 European countries to create a first reference baseline on the degree of climate mainstreaming in local climate plans. This will help to compare the benefits of mainstreaming versus dedicated climate plans, looking at policy effectiveness and ultimately delivery of much needed climate change efforts at the city level. All core cities of the European Urban Audit sample were analyzed, and their local climate plans classified as dedicated or mainstreamed in other local policy initiatives. It was found that the degree of mainstreaming is low for mitigation (9% of reviewed cities; 12% of the identified plans) and somewhat higher for adaptation (10% of cities; 29% of plans). In particular horizontal mainstreaming is a major effort for local authorities; an effort that does not necessarily pay off in terms of success of action implementation. This study concludes that climate change issues in local municipalities are best tackled by either, developing a dedicated local climate plan in parallel to a mainstreamed plan or by subsequently developing first the dedicated and later a mainstreaming plan (joint or subsequent “dual track approach”). Cities that currently provide dedicated local climate plans (66% of cities for mitigation; 26% of cities for adaptation) may follow-up with a mainstreaming approach. This promises effective implementation of tangible climate actions as well as subsequent diffusion of climate issues into other local sector policies. The development of only broad sustainability or resilience strategies is seen as critical.
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- Horellou, Cathy, 1967, et al.
(author)
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The XXL Survey: XXXIV. Double Irony in XXL-North: A tale of two radio galaxies in a supercluster at z = 0.14
- 2018
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
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Journal article (peer-reviewed)abstract
- Aims. We show how the XXL multiwavelength survey can be used to shed light on radio galaxies and their environment. Methods. Two prominent radio galaxies were identified in a visual examination of the mosaic of XXL-North obtained with the Giant Metrewave Radio Telescope at 610 MHz. Counterparts were searched for in other bands. Spectroscopic redshifts from the GAMA database were used to identify clusters and/or groups of galaxies, estimate their masses with the caustic method, and quantify anisotropies in the surrounding galaxy distribution via a Fourier analysis. Results. Both radio galaxies are of FR I type and are hosted by early-type galaxies at a redshift of 0.138. The first radio source, named the Exemplar, has a physical extent of ∼400 kpc; it is located in the cluster XLSSC 112, which has a temperature of ∼2 keV, a total mass of ∼1014 Mo, and resides in an XXL supercluster with eight known members. The second source, named the Double Irony, is a giant radio galaxy with a total length of about 1.1 Mpc. Its core coincides with a cataloged point-like X-ray source, but no extended X-ray emission from a surrounding galaxy cluster was detected. However, from the optical data we determined that the host is the brightest galaxy in a group that is younger, less virialized, and less massive than the Exemplar's cluster. A friends-of-friends analysis showed that the Double Irony's group is a member of the same supercluster as the Exemplar. There are indications that the jets and plumes of the Double Irony have been deflected by gas associated with the surrounding galaxy distribution. Another overdensity of galaxies (the tenth) containing a radio galaxy was found to be associated with the supercluster. Conclusions. Radio Galaxies can be used to find galaxy clusters/groups that are below the current sensitivity of X-ray surveys.
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- Dollet, L, et al.
(author)
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Glutamine Regulates Skeletal Muscle Immunometabolism in Type 2 Diabetes
- 2022
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 71:4, s. 624-636
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Journal article (peer-reviewed)abstract
- Dysregulation of skeletal muscle metabolism influences whole-body insulin sensitivity and glucose homeostasis. We hypothesized that type 2 diabetes–associated alterations in the plasma metabolome directly contribute to skeletal muscle immunometabolism and the subsequent development of insulin resistance. To this end, we analyzed the plasma and skeletal muscle metabolite profile and identified glutamine as a key amino acid that correlates inversely with BMI and insulin resistance index (HOMA-IR) in men with normal glucose tolerance or type 2 diabetes. Using an in vitro model of human myotubes and an in vivo model of diet-induced obesity and insulin resistance in male mice, we provide evidence that glutamine levels directly influence the inflammatory response of skeletal muscle and regulate the expression of the adaptor protein GRB10, an inhibitor of insulin signaling. Moreover, we demonstrate that a systemic increase in glutamine levels in a mouse model of obesity improves insulin sensitivity and restores glucose homeostasis. We conclude that glutamine supplementation may represent a potential therapeutic strategy to prevent or delay the onset of insulin resistance in obesity by reducing inflammatory markers and promoting skeletal muscle insulin sensitivity.
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