Background:
Circadian misalignment, e.g. shift work, is associated with an increased risk to develop obesity and type 2 diabetes. We recently showed that simulated shift work in a laboratory setting leads to skeletal muscle insulin resistance in young healthy volunteers after 3 consecutive nights. Based on previously observed changes in gene expression related to PPAR signalling and fat metabolism, we here aimed to test the hypothesis that a disturbed muscle lipid metabolism contributes to the development of muscle insulin resistance upon circadian misalignment.

Methods:
In a randomized cross-over design, 14 healthy, lean, male volunteers underwent one control (aligned) period and one circadian misalignment period both consisting of ~3.5 days spent in a respiration chamber. In the aligned condition, participants followed a normal diurnal lifestyle, including scheduled sleep from 11PM to 7AM and meals provided at 8AM, 12:30PM, 3PM and 8PM. In the misaligned condition, day and night were rapidly shifted by 12h on day 2. This regime was continued for 2 days before measurements were performed. For each condition, two skeletal muscle biopsies were taken from the m. vastus lateralis at 8AM and 8PM and subjected to semi-targeted lipidomics using UPLC/HRMS.

Results:
Only 2% (19 of 1178) of detected lipids were different between morning and evening in the aligned condition, whereas 9% (102 lipids) displayed a morning-evening difference upon misalignment. The majority of lipids that changed upon misalignment were triacylglycerols, in particular species of a carbon length ≥ 55. Cardiolipins were generally decreased upon misalignment. Cholesterol esters adjusted to the shifted behavior and were hence increased in the fed state of both conditions.

Conclusion:
Our findings show that the skeletal muscle lipidome is disturbed under conditions simulating shift work which may contribute to the muscle insulin resistance upon circadian misalignment.