[1/10]
A thread on our new piece in @FASEBorg
“Circadian misalignment disturbs the skeletal muscle lipidome in healthy young men” #shiftwork
@rhhoutkooper @SchrauwenP
dx.doi.org/10.1096/fj.202…
A thread on our new piece in @FASEBorg
“Circadian misalignment disturbs the skeletal muscle lipidome in healthy young men” #shiftwork
@rhhoutkooper @SchrauwenP
dx.doi.org/10.1096/fj.202…
2/10
Circadian misalignment, as seen in night-shift work, is associated with a ⤴️ risk to develop many different pathologies (see figure below), especially #obesity and type 2 #diabetes are quite common in shift-workers.
tinyurl.com/w2j7kes3
Circadian misalignment, as seen in night-shift work, is associated with a ⤴️ risk to develop many different pathologies (see figure below), especially #obesity and type 2 #diabetes are quite common in shift-workers.
tinyurl.com/w2j7kes3
3/10
Our group @DMRG_UM recently showed that simulating #shiftwork for 3 nights leads to:
➡️ disruption of the core molecular clock
➡️ induction of enhanced lipid metabolism pathways
➡️ insulin resistance in skeletal muscle of young healthy 👨
pnas.org/content/115/30…
Our group @DMRG_UM recently showed that simulating #shiftwork for 3 nights leads to:
➡️ disruption of the core molecular clock
➡️ induction of enhanced lipid metabolism pathways
➡️ insulin resistance in skeletal muscle of young healthy 👨
pnas.org/content/115/30…
4/10
As a follow-up, we wanted to better understand the molecular mechanisms within skeletal muscle underlying the induced insulin resistance.
Therefore, we performed lipidomics & confocal microscopy analysis to study different lipid species & lip droplet morphology in muscle.
As a follow-up, we wanted to better understand the molecular mechanisms within skeletal muscle underlying the induced insulin resistance.
Therefore, we performed lipidomics & confocal microscopy analysis to study different lipid species & lip droplet morphology in muscle.
5/10
Results:
❌ Lipid droplet morphology was not altered upon misalignment at the investigated time points.
✅ Lipidomics revealed that only 2% of detected lipids were different between 🌅vs🌉 upon alignment, whereas 12% displayed a 🌅vs🌉 difference upon misalignment.
Results:
❌ Lipid droplet morphology was not altered upon misalignment at the investigated time points.
✅ Lipidomics revealed that only 2% of detected lipids were different between 🌅vs🌉 upon alignment, whereas 12% displayed a 🌅vs🌉 difference upon misalignment.
6/10
Triacylglycerols of a carbon length of ≥55, were the most abundant lipid species that changed upon misalignment indicating elongation 🐍
Cardiolipins associated with mitochondria were ⤵️ upon misalignment.
Triacylglycerols of a carbon length of ≥55, were the most abundant lipid species that changed upon misalignment indicating elongation 🐍
Cardiolipins associated with mitochondria were ⤵️ upon misalignment.
7/10
Phosphatidylcholines (mostly part of cell membranes) consistently followed the same 🌅vs.🌉pattern, suggesting regulation by the circadian⏲️.
Cholesteryl esters adjusted to the shifted behavior with higher levels in the fed state irrespective of time of day.
Phosphatidylcholines (mostly part of cell membranes) consistently followed the same 🌅vs.🌉pattern, suggesting regulation by the circadian⏲️.
Cholesteryl esters adjusted to the shifted behavior with higher levels in the fed state irrespective of time of day.
8/10
Changes in the diurnal 🌅🌉 pattern of these altered lipid species may contribute to the misalignment-induced insulin resistance.
However, none of the altered lipid species was directly correlated to markers of insulin sensitivity!
Changes in the diurnal 🌅🌉 pattern of these altered lipid species may contribute to the misalignment-induced insulin resistance.
However, none of the altered lipid species was directly correlated to markers of insulin sensitivity!
9/10
Next to such mechanistic studies as ours, we urgently need applied field studies in shift-workers aimed at testing promising intervention strategies, such as timed 🏃♀️🚴♂️, ☀️💡 therapy & fasting regimes, to ⤵️the risk of shift-workers to develop metabolic diseases.
Next to such mechanistic studies as ours, we urgently need applied field studies in shift-workers aimed at testing promising intervention strategies, such as timed 🏃♀️🚴♂️, ☀️💡 therapy & fasting regimes, to ⤵️the risk of shift-workers to develop metabolic diseases.
10/10
Moreover, much better educational work is needed to inform shift-workers of the potential health risks of being involved in shift work over years !!!
Moreover, much better educational work is needed to inform shift-workers of the potential health risks of being involved in shift work over years !!!
Thanks to all people involved in this project, including twitter co-authors:
@NynkePolanen @rhhoutkooper @SchrauwenP @mvanweeghel @JorisHoeks @FredericVaz
@NynkePolanen @rhhoutkooper @SchrauwenP @mvanweeghel @JorisHoeks @FredericVaz
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