Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay

Cécile Vors 1 Laurie Joumard-Cubizolles 2 Manon Lecomte 1 Emmanuel Combe 1 Lemlih Ouchchane 3, 4 Jocelyne Drai 1, 5 Ketsia Raynal 6 Florent Joffre 7 Laure Meiller 8, 1 Mélanie Le Barz 1 Patrice Gaborit 6 Aurélie Caille 9 Monique Sothier 10 Carla Domingues-Costa Faria 2 Adeline Blot 9 Aurélie Wauquier 11 Emilie Blond 1 Valérie Sauvinet 1 Genevieve Gesan-Guiziou 12 Jean-Pierre Bodin 13 Philippe Moulin 1, 14 David Cheillan 1, 15 Hubert Vidal 1 Beatrice Morio 1 Eddy Cotte 16 Françoise Morel-Laporte 9 Martine Laville 1 Annick Bernalier 17 Stéphanie Lambert-Porcheron 18 Corinne Malpuech Brugere 2 Marie-Caroline Michalski 1
Abstract : Objectives: Nutritional strategies can play a major role in the management of cholesterolemia, notably in postmenopausal women at risk of CVD. Interest has recently grown on the potential health benefits of milk polar lipids (MPL).We showed that isolipidic enrichment of the diet with MPL improved several lipid CV risk factors but underlying mechanisms remained unclear. We hypothesized that MPL reduce intestinal cholesterol absorption in humans. Methods:We performed a double-blind randomized controlled trial in 58 postmenopausal women with fasting HDL-cholesterol < 1.6 mM.They were subjected to a 4-week dietary intervention with daily consumption of a cream-cheese containing 12 g of milk fat including either 0 g (control, n = 19), 3 g (n = 19) or 5 g (n = 20) of MPL. Before and after each intervention, blood lipids were measured in the whole cohortwhereas fecal lipids and coprostanol were analyzed in a subgroup (n = 7–9 per group). A proof-of-concept mechanistic crossover study was also carried out in 4 ileostomized subjects who performed 8hpostprandial tests after consuming 0g-, 3g- or 5g-MPL enriched cheese labelled with 2H-cholesterol tracer. Plasma, chylomicrons and ileal efflux were analyzed. Results: Milk fat enriched with 3 to 5 g MPL induced doseresponse reductions in serum total cholesterol (up to −6.8% in 5 g group, p < 0.05), LDL-cholesterol (−8.7%, p < 0.05) and HDL/total-cholesterol ratio (p < 0.001), compared to the control that had no effect. Fecal excretion of coprostanol increased after MPL supplementation (p < 0.05, 3g- and 5g-MPL vs control), and the fecal coprostanol/cholesterol ratio was inversely correlated with serum total- and LDL-cholesterol after intervention (r = −0.5, p < 0.05). In ileostomized subjects, postprandial accumulation of 2Hcholesterol in plasma and chylomicrons was reduced after 3 to 5 g MPL consumption (p < 0.05, vs control). Both cholesterol and milk sphingomyelin increased in ileal efflux after MPL enriched cheeses (p < 0.05). Conclusions: Present results suggest that milk polar lipids decrease cholesterol absorption in humans through interactions with sphingomyelin and by increasing conversion of cholesterol to coprostanol. Funding Sources: ANR (French National Research Agency, VALOBAB project, ANR-11-ALID-007–01), PHRC-I (French Clinical Research Program, 14–007), CNIEL (French Dairy Interbranch Organization).
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Cécile Vors, Laurie Joumard-Cubizolles, Manon Lecomte, Emmanuel Combe, Lemlih Ouchchane, et al.. Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay. Nutrition 2019, Jun 2019, Baltimore, United States. 3 (supplément 1 juin 2019), 2019, Current Developments in Nutrition. ⟨10.1093/cdn/nzz031.P06-041-19⟩. ⟨hal-02269491⟩



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