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

  • Jakob Wefers (Creator)
  • Dirk van Moorsel (Creator)
  • Jan Hansen (Creator)
  • Guido Hooiveld (Creator)
  • Sander Kersten (Creator)
  • Patrick Schrauwen (Creator)

Dataset

Description

Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes, however, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and muscle molecular circadian clock have never been investigated in humans. Here we investigated insulin sensitivity and muscle metabolism in fourteen healthy young lean men (age 22.4 ± 2.8 years; BMI 22.3 ± 2.1 kg/m2 [mean ± SD]) after a 3-day control protocol and a 3.5-day misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that circadian misalignment results in a significant decrease in peripheral insulin sensitivity due to a reduced skeletal muscle non-oxidative glucose disposal (Rate of disappearance: 23.7 ± 2.4 vs. 18.4 ± 1.4 mg/kg/min; control vs. misalignment; p=0.024). Fasting glucose and FFA levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the new behavourial rhythm, and microarray analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misallignement. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.
Date made available10 Aug 2018
PublisherWageningen University

Research Output

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

Wefers, J., van Moorsel, D., Hansen, J., Connell, N. J., Havekes, B., Hoeks, J., van Marken Lichtenbelt, W. D., Duez, H., Phielix, E., Kalsbeek, A., Boekschoten, M. V., Hooiveld, G. J., Hesselink, M. K. C., Kersten, S., Staels, B., Scheer, F. A. J. L. & Schrauwen, P., 24 Jul 2018, In : Proceedings of the National Academy of Sciences of the United States of America. 115, 30, p. 7789-7794

Research output: Contribution to journalArticleAcademicpeer-review

Open Access
  • 39 Citations (Scopus)

    Cite this

    Wefers, J. (Creator), van Moorsel, D. (Creator), Hansen, J. (Creator), Hooiveld, G. J. E. J. (Creator), Kersten, A. H. (Creator), Schrauwen, P. (Creator) (10 Aug 2018). Circadian misalignment induces fatty acid metabolism gene profiles and induces insulin resistance in human skeletal muscle. Wageningen University.