Comparative lipidomics reveals compositional differences between yak and cattle-yak milk

Yak and cattle-yak milk are important dairy resources in high-altitude regions, but their lipidomic differences remain poorly characterized. The objective of this study was to compare the milk lipid profiles of 5 Tibetan yak groups and 2 cattle-yak groups produced under plateau conditions. Milk lipids were analyzed by liquid chromatography-tandem mass spectrometry, followed by multivariate analysis, differential lipid screening, and pathway enrichment analysis. A total of 901 lipid species were identified, with glycerophospholipids representing the largest proportion of detected lipids. Multivariate analysis showed distinct lipidomic profiles between yak and cattle-yak milk. Among the 5 yak groups, 28 differential lipids were identified, mainly involving glycerophospholipids, sphingolipids, glycerolipids, and fatty acyl-related molecules. No false discovery rate-confirmed differential lipids were detected between Holstein × yak and Jersey × yak milk, although exploratory analysis suggested group-associated lipid variation. Comparison between yak and cattle-yak milk identified 18 differential lipids after accounting for breed nested within animal type. These lipids were mainly related to membrane-associated polar lipids and glycerolipids. Pathway analysis indicated that glycerophospholipid metabolism was the main pathway distinguishing yak and cattle-yak milk, with additional evidence for fatty acid- and glycerolipid-related differences. A panel of false discovery rate-adjusted lipids showed potential for discriminating among the 7 milk groups, supporting their use as candidate lipid signatures for milk-group characterization. Overall, these findings provide a lipidomic basis for evaluating plateau dairy resources, but broader validation under more controlled production conditions is needed before these lipid signatures can be applied to milk quality assessment or product development.