Abstract

The innate biologic clock plays a significant role in lipid metabolism, including the peripheral clock in the pancreas. However, an evaluation of the downstream lipids in the pancreatic lipidome is lacking. We sought to understand the diurnal variations of lipids within the pancreatic lipidome. At 4 weeks of age, C57Bl/6J mice were subjected to either normal lighting conditions or a chronic jetlag (CJ) condition known to mimic chronic shiftwork in humans. At 9 months, mice were serially killed at 4-hour intervals for 24 hours. The pancreas was removed and subjected to untargeted liquid chromatography-mass spectrometry to examine the pancreatic lipidome. A total of 4.7% of the pancreatic lipidome was rhythmically expressed, which increased to 12.9% after CJ. After CJ, there was a 4.58-hour shift in the timing of peak 24-hour lipid expression. Chronic jetlag also led to the enrichment of diacylglycerols and triglycerides, while promoting a decrease in lysophosphatidylcholines and 44-carbon acyl chain lipids. The pancreatic lipidome exhibits diurnal rhythmicity across a broad number of lipid classes. Chronic jetlag led to alterations in lipid composition that mirrored other metabolically active organs. Several of the reported changes may link altered sleep-wake cycles with known circadian disruption-induced pancreatic diseases.

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