Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle

Jakob Wefers (1, 2) , Dirk van Moorsel (1, 2) , Jan Hansen (2) , Niels Connell (2) , Bas Havekes (3) , Joris Hoeks (4) , Wouter van Marken Lichtenbelt (5, 4) , Hélène Duez (6, 7) , Esther Phielix (4) , Andries Kalsbeek (8) , Mark Boekschoten (9, 10) , Guido Hooiveld (4) , Matthijs Hesselink (4) , Sander Kersten (11) , Bart Staels (6, 12, 7) , Frank Scheer (13) , Patrick Schrauwen (4)

1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
2 Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands;
3 MUMC - Maastricht University Medical Centre
4 Maastricht University [Maastricht]
5 NUTRIM School for Nutrition and Translational Research in Metabolism
6 RNMCD - Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011
7 RNMCD - Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011
8 Netherlands Institute for Brain Research
9 Division of Human Nutrition
10 TIFN - Top Institute Food and Nutrition
11 Nutrition, Metabolism and Genomics Group [Wageningen, The Netherlands]
12 EGID - Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508
13 HMS - Harvard Medical School [Boston]

Significance Shift workers are affected by circadian misalignment and have an increased risk to develop metabolic diseases such as type 2 diabetes. Here, we show that during simulated short-term night shift work insulin sensitivity at the level of skeletal muscle is decreased in male volunteers, which could contribute to the development of type 2 diabetes in the long term. We also find that the muscle molecular clock does not align rapidly to the new behavioral cycle. Importantly, on the level of the transcriptome, circadian misalignment induced upregulation of fatty acid metabolism pathways, potentially resulting in substrate competition on the cellular level. These findings help to better understand the negative consequences during night shift work.

Domaines: Sciences du Vivant [q-bio]

Jakob Wefers, Dirk van Moorsel, Jan Hansen, Niels Connell, Bas Havekes, et al.. Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115 (30), pp.7789-7794. ⟨10.1073/pnas.1722295115⟩. ⟨hal-04463033⟩