Fasting increases 18:2-containing phosphatidylcholines to complement the decrease in 22:6-containing phosphatidylcholines in mouse skeletal muscle

Fasting stimulates catabolic reactions in skeletal muscle to survive nutrient deprivation. Cellular phospholipids have large structural diversity due to various polar-heads and acyl-chains that affect many cellular functions. Skeletal muscle phospholipid profiles have been suggested to be associated with muscle adaptations to nutritional and environmental status. However, the effect of fasting on skeletal muscle phospholipid profiles remains unknown. Here, we analyzed phospholipids using liquid chromatography mass spectrometry. We determined that fasting resulted in a decrease in 22:6-containing phosphatidylcholines (PCs) (22:6-PCs) and an increase in 18:2-containing PCs (18:2-PCs). The fasting-induced increase in 18:2-PCs was sufficient to complement 22:6-PCs loss, resulting in the maintenance of the total amount of polyunsaturated fatty acid (PUFA)-containing PCs. Similar phospholipid alterations occurred in insulin-deficient mice, which indicate that these observed phospholipid perturbations were characteristic of catabolic skeletal muscle. In lysophosphatidic acid acyltransferase 3-knockout muscles that mostly lack 22:6-PCs, other PUFA-containing PCs, mainly 18:2-PCs, accumulated. This suggests a compensatory mechanism for skeletal muscles to maintain PUFA-containing PCs.

Automated summary

The study found that fasting led to a decrease in 22:6-phosphatidylcholines (PCs) and an increase in 18:2-PCs in skeletal muscle phospholipid profiles. This increase in 18:2-PCs during fasting was able to compensate for the loss of 22:6-PCs, maintaining the total amount of polyunsaturated fatty acid (PUFA)-containing PCs. Similar phospholipid alterations were observed in insulin-deficient mice, indicating that these perturbations were characteristic of catabolic skeletal muscle. In muscles lacking 22:6-PCs, such as lysophosphatidic acid acyltransferase 3 knockout mice, accumulation of other PUFA-containing PCs, mainly 18:2-PCs, suggests a compensatory mechanism for maintaining PUFA-containing PCs in skeletal muscle.