Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity

The authors are supported by grants from the Novo Nordisk Foundation (NNF14OC0011493, NNF17OC0030088 and NNF14OC0009941), Swedish Diabetes Foundation (DIA2018-357, DIA2018-336), Swedish Research Council (2015-00165, 2018-02389), the Strategic Research Program in Diabetes at Karolinska Institutet (2009-1068), the Stockholm County Council (SLL20150517, SLL20170159), the Swedish Research Council for Sport Science (P2018-0097), and the EFSD European Research Programme on New Targets for Type 2 Diabetes supported by an educational research grant from MSD. L.D. was supported by a Novo Nordisk postdoctoral fellowship run in partnership with Karolinska Institutet. B.M.G. was supported by a fellowship from the Wenner-Gren Foundation (Sweden). N.J.P. was supported by an Individual Fellowship from the Marie Skłodowska-Curie Actions (European Commission, 704978, 675610) and grants from the Sigurd och Elsa Goljes Minne and Lars Hiertas Minne Foundations (Sweden). D.J.B. was supported by the ANZ Mason Foundation and Australian Research Council Discovery Program (ARC DP140104165). Additional support was received from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen (NNF18CC0034900) (to J.R.Z.). We thank Dr. Nanjiang Shu from National Bioinformatics Infrastructure Sweden (NBIS) for setting up the web-server. We also thank EGI federated cloud for providing the computer resource for hosting the web-server. We acknowledge the Beta Cell in-vivo Imaging/Extracellular Flux Analysis core facility supported by the Strategic Research Program (SRP) in Diabetes for the usage of the Seahorse flux analyzer. Open access funding provided by Karolinska Institute.Peer reviewedPublisher PD

Comparative profiling of skeletal muscle models reveals heterogeneity of transcriptome and metabolism

We acknowledge the Beta Cell in-vivo Imaging/Extracellular Flux Analysis core facility, supported by the Strategic Research Program (SRP) in Diabetes, for the use of the Seahorse flux analyzer. AUTHOR CONTRIBUTIONS A.M.A. and N.J.P. conceived and designed research; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., and N.J.P. performed experiments; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., and N.J.P. analyzed data; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., A.K., J.R.Z., and N.J.P. interpreted results of experiments; A.M.A. and N.J.P. prepared figures; A.M.A. and N.J.P. drafted manuscript; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., A.K., J.R.Z., and N.J.P. edited and revised manuscript; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., A.K., J.R.Z., and N.J.P. approved final version of manuscript.Peer reviewedPublisher PD

Palmitate impairs circadian transcriptomics in muscle cells through histone modification of enhancers

Acknowledgements The authors are supported by grants from the Novo Nordisk Foundation (NNF14OC0011493 and NNF17OC0030088), EFSD/Novo Nordisk Foundation Future Leader Award (NNF21SA0072747), Swedish Diabetes Foundation (DIA2021-641 and DIA2021-645), Swedish Research Council (2015-00165 and 2018-02389), KID-funding (2-3591/2014), the Strategic Research Program in Diabetes at Karolinska Institutet (2009-1068), Marie Skłodowska-Curie Actions (European Commission, 675610 and 704978), and Novo Nordisk postdoctoral fellowship run in partnership with Karolinska Institutet. Additional support was received from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen (NNF18CC0034900).Peer reviewedPublisher PD

Disrupted circadian oscillations in type 2 diabetes are linked to altered rhythmic mitochondrial metabolism in skeletal muscle

Funding: The authors are supported by grants from the AstraZeneca SciLifeLab Research Programme, Novo Nordisk Foundation (NNF14OC0011493, and NNF17OC0030088), Swedish Diabetes Foundation (DIA2018-357), Swedish Research Council (2015-00165 and 2018-02389), the Knut and Alice Wallenberg Foundation (2018-0094), the Strategic Research Programme in Diabetes at Karolinska Institutet (2009-1068), the Stockholm County Council (SLL20170159), and the Swedish Research Council for Sport Science (P2019-0140). B.M.G. was supported by fellowships from the Novo Nordisk Foundation (NNF19OC0055072), the Wenner-Gren Foundation, an Albert Renold Travel Fellowship from the European Foundation for the Study of Diabetes, and an Eric Reid Fund for Methodology from the Biochemical Society. N.J.P. and L.S.-P. were supported by an Individual Fellowship from the Marie Skłodowska-Curie Actions (European Commission: 704978 and 675610). X.Z. and K.A.E. were supported by NIH R01AR066082. N.J.P. was supported by grants from the Sigurd och Elsa Goljes Minne and Lars Hierta Memorial Foundations (Sweden). We acknowledge the Beta Cell in-vivo Imaging/Extracellular Flux Analysis core facility supported by the Strategic Research Program in Diabetes for the usage of the Seahorse flux analyzer. Additional support was received from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen (NNF18CC0034900). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation. We acknowledge the Single-Cell Omics platform at the Novo Nordisk Foundation Center for Basic Metabolic Research for technical and computational expertise and support. Schematics are created with BioRender.com.Peer reviewedPublisher PD

A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening

Many favorable metabolic effects have been attributed to thermogenic activity of brown adipose tissue (BAT). Yet, time of day has rarely been considered in this field of research. Here, we show that a diurnal rhythm in BAT activity regulates plasma lipid metabolism. We observed a high-amplitude rhythm in fatty acid uptake by BAT that synchronized with the light/dark cycle. Highest uptake was found at the onset of the active period, which coincided with high lipoprotein lipase expression and low angiopoietin-like 4 expression by BAT. Diurnal rhythmicity in BAT activity determined the rate at which lipids were cleared from the circulation, thereby imposing the daily rhythm in plasma lipid concentrations. In mice as well as humans, postprandial lipid excursions were nearly absent at waking. We anticipate that diurnal BAT activity is an important factor to consider when studying the therapeutic potential of promoting BAT activity. van den Berg et al. show a strong circadian rhythm in fatty acid uptake by brown adipose tissue that peaks at wakening regardless of the light exposure period. Consequently, postprandial lipid handling by brown adipose tissue is highest at wakening, resulting in the lowest postprandial plasma lipid excursions