Wefers 2018 Proc Natl Acad Sci U S A

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Wefers J, van Moorsel D, Hansen J, Connell NJ, Havekes B, Hoeks J, van Marken Lichtenbelt WD, Duez H, Phielix E, Kalsbeek A, Boekschoten MV, Hooiveld GJ, Hesselink MKC, Kersten S, Staels B, Scheer FAJL, Schrauwen P (2018) Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle. Proc Natl Acad Sci U S A 115:7789-94.

» PMID: 29987027 Open Access

Wefers J, van Moorsel D, Hansen J, Connell NJ, Havekes B, Hoeks J, van Marken Lichtenbelt WD, Duez H, Phielix E, Kalsbeek A, Boekschoten MV, Hooiveld GJ, Hesselink MKC, Kersten S, Staels B, Scheer FAJL, Schrauwen P (2018) Proc Natl Acad Sci U S A

Abstract: 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 the muscle molecular circadian clock have never been studied in humans. Here, we investigated insulin sensitivity and muscle metabolism in 14 healthy young lean men [age 22.4 ± 2.8 years; body mass index (BMI) 22.3 ± 2.1 kg/m2 (mean ± SD)] after a 3-d control protocol and a 3.5-d misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that short-term circadian misalignment results in a significant decrease in muscle insulin sensitivity due to a reduced skeletal muscle nonoxidative glucose disposal (rate of disappearance: 23.7 ± 2.4 vs. 18.4 ± 1.4 mg/kg per minute; control vs. misalignment; P = 0.024). Fasting glucose and free fatty acid 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 inverted behavioral cycle, and transcriptome analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misalignment. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.

Keywords: Circadian misalignment, Diabetes, Insulin sensitivity, Shift work, Skeletal muscle Bioblast editor: Plangger M, Kandolf G O2k-Network Lab: NL Maastricht Schrauwen P, FR Lille Duez H


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Diabetes 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Intact cells  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase 

Coupling state: OXPHOS, ET  Pathway: F, N  HRR: Oxygraph-2k 

Labels, 2018-08