Dietary Intake of a Milk Sphingolipid-Rich MFGM/EV Concentrate Ameliorates Age-Related Metabolic Dysfunction

Background/Objectives: Nutraceuticals containing milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are purported to abate age-related metabolic dysfunction due to their richness in milk sphingolipids. As such, nutraceuticals offer a compelling strategy to improve metabolic health through dietary means, especially for elderly persons who are unable to adhere to common therapeutic interventions. To address this, we examined the effects of supplementing aged sedentary rats with an MFGM/EV-rich concentrate. Methods/Results: In a 25-week study, 89-week-old male rats received either a milk sphingolipid-rich MFGM/EV concentrate or a control supplement. Analysis of metabolic health using a battery of tests, including MS^ALL lipidomics of plasma, liver, and other peripheral tissues, revealed that MFGM/EV supplementation promotes accretion of unique sphingolipid signatures, ameliorates ceramide biomarkers predictive of cardiovascular death, and has a general lipid-lowering effect. At the functional level, we find that these health-promoting effects are linked to increased lipoprotein particle turnover, showcased by reduced levels of triglyceride-rich particles, as well as a metabolically healthier liver, assessed using whole-body lipidomic flux analysis. Conclusions: Altogether, our work unveils that MFGM/EV-containing food holds a potential for ameliorating age-related metabolic dysfunction in elderly individuals.