Lipidomic perspectives on the role of lactosylceramides in inflammation and disease: A narrative review.

BACKGROUND: Lactosylceramides (LacCers) are glycosphingolipids that play essential roles in physiological and pathological processes across immune, endocrine, and neurological systems, with mechanistic studies demonstrating that LacCers modulate inflammatory signalling, oxidative stress responses, membrane microdomain organisation, and control aspects of mitochondrial function. Historically, LacCers were quantified predominantly as a total lipid subclass, limiting the ability to discern how individual species contribute to biological processes in clinical contexts. Recent advances in mass spectrometry based lipidomics now enable LacCer species to be resolved by acyl-chain length and saturation, offering far greater biochemical and clinical insights.

METHODS: In this narrative review, we examine evidence from population based lipidomic studies describing how LacCer composition varies across healthy and diseased states.

RESULTS: In metabolic and vascular disorders, multiple studies report elevations in specific short- and medium-chain LacCer species, whereas patterns involving longer-chain species appear more heterogeneous. Altered LacCer profiles have also been described in neurodegenerative disease, chronic kidney disease, and cancers, with species-level differences varying by disease-context, tissue type, and analytical platform.

CONCLUSIONS: Our findings describe disease- and tissue-specific variations in LacCer acyl-chain composition, underscoring the value of species-level resolution for mechanistic understanding and informing the application of LacCer profiles in future biomarker and therapeutic studies.