D1 | Abstract 06

Annual NUTRIM Symposium 18 November 2020


Circadian misalignment disturbs the lipidome in human skeletal muscle

Jan-Frieder Harmsen1, Nynke van Polanen1, Jakob Wefers1, Michel van Weeghel², Joris Hoeks1, Jan Hansen1, Frédéric M. Vaz², Mia L. Pras-Raves², Gert Schaart1, Dirk van Moorsel1, Matthijs K. C. Hesselink1, Riekelt H. Houtkooper² and Patrick Schrauwen1

1Department of Nutrition and Movement Sciences, Maastricht University Medical Center
2Laboratory Genetic Metabolic Diseases, Amsterdam UMC
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.

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.

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.

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.

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