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- Wang, Z., et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)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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- Reckien, D., et al.
(författare)
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Dedicated versus mainstreaming approaches in local climate plans in Europe
- 2019
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Ingår i: Renewable & sustainable energy reviews. - : Elsevier. - 1364-0321 .- 1879-0690. ; 112, s. 948-959
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Glund, S., et al.
(författare)
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Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:6, s. 1630-7
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity. Elevated plasma levels of IL-6 are observed in insulin-resistant states. Interestingly, plasma IL-6 levels also increase during exercise, with skeletal muscle being the predominant source. Thus, IL-6 has also been suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P < 0.05). A 30-min pre-exposure to IL-6 did not affect insulin-stimulated glucose transport. IL-6 also increased skeletal muscle glucose incorporation into glycogen, as well as glucose oxidation (1.5- and 1.3-fold, respectively; P < 0.05). IL-6 increased phosphorylation of STAT3 (signal transducer and activator of transcription 3; P < 0.05), AMP-activated protein kinase (P = 0.063), and p38 mitogen-activated protein kinase (P < 0.05) and reduced phosphorylation of S6 ribosomal protein (P < 0.05). In contrast, phosphorylation of protein kinase B/Akt, AS160 (Akt substrate of 160 kDa), and GSK3alpha/beta (glycogen synthase kinase 3alpha/beta) as well as insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity remained unaltered. In conclusion, acute IL-6 exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure.
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| 10. |
- Pillon, NJ, et al.
(författare)
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Palmitate impairs circadian transcriptomics in muscle cells through histone modification of enhancers
- 2022
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Ingår i: Life science alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and elevated circulating lipids may impair metabolism by disrupting the molecular circadian clock. We tested the hypothesis that lipid overload may interact with the circadian clock and alter the rhythmicity of gene expression through epigenomic mechanisms in skeletal muscle. Palmitate reprogrammed the circadian transcriptome in myotubes without altering the rhythmic mRNA expression of core clock genes. Genes with enhanced cycling in response to palmitate were associated with post-translational modification of histones. The cycling of histone 3 lysine 27 acetylation (H3K27ac), a marker of active gene enhancers, was modified by palmitate treatment. Chromatin immunoprecipitation and sequencing confirmed that palmitate exposure altered the cycling of DNA regions associated with H3K27ac. The overlap between mRNA and DNA regions associated with H3K27ac and the pharmacological inhibition of histone acetyltransferases revealed novel cycling genes associated with lipid exposure of primary human myotubes. Palmitate exposure disrupts transcriptomic rhythmicity and modifies enhancers through changes in histone H3K27 acetylation in a circadian manner. Thus, histone acetylation is responsive to lipid overload and may redirect the circadian chromatin landscape, leading to the reprogramming of circadian genes and pathways involved in lipid biosynthesis in skeletal muscle.
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