Probing the transcriptome response to shivering in skeletal muscle using a multilayered bioinformatics approach

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Cold acclimation holds therapeutic potential for improving metabolic health. We previously demonstrated that repeated cold-induced shivering enhances insulin sensitivity in humans. However, the molecular pathways that underlie the skeletal muscle shivering response, and how these relate to beneficial physiological effects, remain poorly understood. In this study, we combined complementary bioinformatics approaches to allow in-depth analysis of the transcriptomic response of human skeletal muscle to repeated shivering. We identified a robust transcriptional signature and show a sex-specific component in the shivering skeletal muscle response, which seemed to diminish following cold adaptation. Our findings provide mechanistic insights into cold-induced muscle adaptations, shed light on potential interesting molecular targets for further investigation, and emphasize the importance of including both sexes in future cold acclimation studies.

Authors 8

1. Rosalie Baak

   University Medical Center Utrecht

   Affiliation as printed

   Center for Molecular Medicine (CMM), UMC Utrecht, The Netherlands

2. Guido J. E. J. Hooiveld

   Wageningen University & Research

   Affiliation as printed

   Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands

3. Patrick Schrauwen Aachen Department of Clinical Epidemiology

   Leiden University · Leiden University Medical Center · Deutsches Diabetes-Zentrum e.V. · German Center for Diabetes Research · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden, University Medical Centre, Leiden, The Netherlands

   German Center for Diabetes Research (DZD), Partner Düsseldorf, Neuherberg, Germany

   Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany

4. Joris Hoeks

   Maastricht University · Deutsches Diabetes-Zentrum e.V. · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands

   Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany

5. Reinier Raymakers
   Affiliation as printed

   DCDC-Tx B.V., Vught, The Netherlands

6. Anja van de Stolpe
   Affiliation as printed

   DCDC-Tx B.V., Vught, The Netherlands

7. Sander Kersten

   Cornell University · Wageningen University & Research

   Affiliation as printed

   Division of Nutritional Sciences, Cornell University, Ithaca, New York, The United States

   Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands

8. Eric Kalkhoven corresponding

   University Medical Center Utrecht

   Affiliation as printed

   Center for Molecular Medicine (CMM), UMC Utrecht, The Netherlands