Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women

International audienceBACKGROUND. High circulating levels of ceramides (Cer) and sphingomyelins (SM) have been associated with cardiometabolic diseases. The consumption of whole-fat dairy products, which naturally contain such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown. We investigated how milk PL supplementation impacts circulating and intestinal SM and Cer composition in association with improvement of cardiovascular markers.METHODS. In a 4 week-randomized double-blind controlled study, 58 postmenopausal women consumed daily a cream cheese containing 0, 3 or 5 g of milk PL. Postprandial metabolic explorations were performed before and after the supplementation. SM and Cer species were analyzed in serum, intestine-derived chylomicrons and feces. The ileal content of 4 ileostomy patients was also explored after milk PL intake in a crossover double-blind study.RESULTS. Milk PL consumption decreased serum atherogenic C24:1 Cer (Pgroup = 0.033), C16:1 (Pgroup = 0.007) and C18:1 (Pgroup = 0.003) SM species. Changes in serum C16+18 SM species were positively correlated with the reduction of total cholesterol (r = 0.706, P < 0.001), LDL-C (r = 0.666, P < 0.001) and ApoB (r = 0.705, P < 0.001). Milk PL decreased the concentration in chylomicrons of total SM (Pgroup < 0.0001) and of C24:1 Cer (Pgroup = 0.001). Saturated SM and Cer species, which are also the major species found in milk PL-enriched cheeses, increased in ileal efflux and feces. There was a marked increase in total fecal Cer after milk PL supplementation (Pgroup = 0.0002). Milk PL also modulated the abundance of some specific SM and Cer species in ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.CONCLUSION. These data demonstrate that milk PL supplementation decreases atherogenic SM and Cer species associated with an improvement of cardiovascular risk markers. Our findings bring new insights on sphingolipid metabolism in the gastrointestinal tract, especially Cer as such signaling molecules potentially participating in the beneficial effect of milk PL. ClinicalTrials.gov, NCT02099032, NCT02146339

Milk polar lipids affect [i]in vitro[/i] digestive lipolysis and postprandial lipid metabolism in mice

Background:Polar lipid (PL) emulsifiers such as milk PLs (MPLs) may affect digestion and subsequent lipid metabolism,but focused studies on postprandial lipemia are lacking.Objective:We evaluated the impact of MPLs on postprandial lipemia in mice and on lipid digestion in vitro.Methods:Female Swiss mice were gavaged with 150mL of oil-in-water emulsion stabilized with 5.7 mg of either MPLs or soybean PLs (SPLs) and killed after 1, 2, or 4 h. Plasma lipids were quantified and in the small intestine, gene expression was analyzed by reverse transcriptase–quantitative polymerase chain reaction. Emulsions were lipolyzed in vitro using a static human digestion model; triglyceride (TG) disappearance was followed by thin-layer chromatography. Results:In mice, after 1 h, plasma TGs tended to be higher in the MPL group than in the SPL group (141 mg/mL vs. 90mg/mL; P = 0.07) and nonesterified fatty acids (NEFAs) were significantly higher (64 mg/mL vs. 44 mg/mL;P < 0.05). The opposite was observed after 4 h with lower TGs (21 mg/mL vs. 35 mg/mL; P < 0.01) and NEFAs (20 mg/mL vs. 32 mg/mL; P < 0.01) in the MPL group compared with the SPL group. This was associated at 4 h with a lower gene expression of apolipoprotein B ( Apob) and Secretion Associated, Ras related GTPase 1 gene homolog B ( Sar1b ), in the duodenum of MPL mice compared with SPL mice ( P < 0.05). Invitro, during the intestinal phase, TGs were more hydrolyzed in the MPL emulsion compared with the SPL emulsion (decremental AUC was 1750%/min vs. 180%/min; P < 0.01). MPLs enhance lipid intestinal hydrolysis and promote more rapid intestinal lipidabsorption and sharper kinetics of lipemia.Conclusions:Postprandial lipemia in mice can be modulated by emulsifying with MPLs compared with SPLs, partlythrough differences in chylomicron assembly, and TG hydrolysis rate as observed in vitro. MPLs may thereby contribute to the long-term regulation of lipid metabolism