Phosphatidylcholine Transfer Protein Attenuates High Fat Diet Induced Changes in Mitochondrial Membrane Phosphatidylcholine Composition

Abstract

Phosphatidylcholine transfer protein (PC‐TP) is a phospholipid binding protein that is enriched in liver and catalyzes intermembrane exchange of phosphatidylcholines (PCs) in vitro. Because it associates with the mitochondria, we explored the hypothesis that PC‐TP regulates the distribution of PC molecular species in mitochondrial membranes. Pctp−/− and Pctp+/+ mice were fed chow or high fat diets. Liver mitochondria were purified and membrane lipid extracts were analyzed by tandem mass spectrometry. The distribution of PC species was determined by precursor ion scanning of m/z 184, which corresponds to the headgroup. In chow fed mice, PC‐TP expression did not influence the distribution of PCs. High fat fed Pctp+/+ mice exhibited a modest 21% decrease in mitochondrial 16:0–18:2 PC and a 27% increase in 16:0–20:4 PC. By contrast, high fat feeding of Pctp−/− mice led to more pronounced changes in the same PCs, with a 43% decrease in 16:0–18:2 PC and 34% increase in 16:0–20:4 PC. We conclude that under physiological conditions, PC‐TP expression is not a determinant of the PC composition of mitochondrial membranes. In response to dietary fat, PC‐TP expression mitigates the enrichment of mitochondria with polyunsaturated PCs, which may modulate biophysical properties of the membrane. Supported by NIH.