Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women
Mélanie Le Barz, … , David Cheillan, Marie-Caroline Michalski
Mélanie Le Barz, … , David Cheillan, Marie-Caroline Michalski
Published April 15, 2021
Citation Information: JCI Insight. 2021;6(10):e146161. https://doi.org/10.1172/jci.insight.146161.
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Clinical Medicine Clinical trials Metabolism

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

Abstract

BACKGROUND High circulating levels of ceramides (Cer) and sphingomyelins (SM) are associated with cardiometabolic diseases. The consumption of whole fat dairy products, naturally containing such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown.METHODS In a 4-week randomized controlled trial, 58 postmenopausal women daily consumed milk PL-enriched cream cheese (0, 3, or 5 g of milk PL). Postprandial metabolic explorations were performed before and after supplementation. Analyses included SM and Cer species in serum, chylomicrons, and feces. The ileal contents of 4 ileostomy patients were also explored after acute milk PL intake.RESULTS Milk PL decreased serum atherogenic C24:1 Cer, C16:1 SM, and C18:1 SM species (Pgroup < 0.05). Changes in serum C16+18 SM species were positively correlated with the reduction of cholesterol (r = 0.706), LDL-C (r = 0.666), and ApoB (r = 0.705) (P < 0.001). Milk PL decreased chylomicron content in total SM and C24:1 Cer (Pgroup < 0.001), parallel to a marked increase in total Cer in feces (Pgroup < 0.001). Milk PL modulated some specific SM and Cer species in both ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.CONCLUSION Milk PL supplementation decreased atherogenic SM and Cer species associated with the improvement of cardiovascular risk markers. Our findings bring insights on sphingolipid metabolism in the gut, especially Cer, as signaling molecules potentially participating in the beneficial effects of milk PL.TRIAL REGISTRATION ClinicalTrials.gov, NCT02099032, NCT02146339.FUNDING ANR-11-ALID-007-01; PHRCI-2014: VALOBAB, no. 14-007; CNIEL; GLN 2018-11-07; HCL (sponsor).

Authors

Mélanie Le Barz, Cécile Vors, Emmanuel Combe, Laurie Joumard-Cubizolles, Manon Lecomte, Florent Joffre, Michèle Trauchessec, Sandra Pesenti, Emmanuelle Loizon, Anne-Esther Breyton, Emmanuelle Meugnier, Karène Bertrand, Jocelyne Drai, Chloé Robert, Annie Durand, Charlotte Cuerq, Patrice Gaborit, Nadine Leconte, Annick Bernalier-Donadille, Eddy Cotte, Martine Laville, Stéphanie Lambert-Porcheron, Lemlih Ouchchane, Hubert Vidal, Corinne Malpuech-Brugère, David Cheillan, Marie-Caroline Michalski

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Figure 2

Major correlations between the impacts of milk PL supplementation on blood lipids and on serum SM and Cer (VALOBAB-C).

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Major correlations between the impacts of milk PL supplementation on blo...
(A–C, and G) Spearman’s correlations between blood lipids and serum SM and Cer species. All data are expressed as ΔV2–V1 at fasting. Yellow, all groups were considered for the analysis (A and G) (n = 30); blue, the 2 groups supplemented with either 3 or 5 g–milk PL only (n = 20); and orange, the control group only (n = 10). For panels A–C, and G, asterisks in bold represent correlations that remain significant after adjustment for clinical center, quartiles of volunteer age, and waist circumference. (D–F and H–K) Graphs illustrating specific Spearman’s correlations between the intervention impact on C16+18 SM species and on LDL-C (D), total C (E), and ApoB48 (F); between C20+22 Cer species proportions (%) and LDL-C (H), and total C (I); between C24-26 Cer species proportions (%) and LDL-C (J), and total C (K). Apo, apolipoprotein; C, cholesterol; Cer, ceramides; CTL, control; HDL, high density lipoprotein; LDL, low density lipoprotein; NEFA, nonesterified fatty acids; PL, polar lipids; SM, sphingomyelin; TAG, triacylglycerols.