Intestinal absorption of sphingosine: new insights on generated ceramide species using stable isotope tracing in vitro.

Dietary sphingomyelin (SM) has been reported to favorably modulate postprandial lipemia. Mechanisms underlying these beneficial effects on cardiovascular risk markers are not fully elucidated. Rodent studies showed that tritiated SM was hydrolyzed in the intestinal lumen into ceramides (Cer), and further to sphingosine (SPH) and fatty acids (FA) that were absorbed by the intestine. Our objective was to investigate in Caco-2/TC7 cells cultured on semi-permeable inserts the uptake and metabolism of SPH and/or C23:0, the main FA of milk SM, as well as lipid secretion. Mixed micelles (MM) consisting of different digested lipids and taurocholate were prepared without or with SPH, SPH and C23:0 (SPH+C23:0) or C23:0. Triglycerides (TG) were quantified in the basolateral medium and sphingolipids were analyzed by tandem mass spectrometry. TG secretion increased 11-fold in all MM-incubated cells compared with lipid-free medium. Apical supply of SPH-enriched MM led to increased concentrations of total Cer in cells and co-addition of C23:0 in SPH-enriched MM led to a preferential increase of C23:0 Cer and C23:0 SM. Complementary experiments using deuterated SPH demonstrated that SPH-d9 was partly converted to sphingosine-1-phosphate-d9, Cer-d9 and SM-d9 within cells incubated with SPH-enriched MM. A few Cer-d9 (2% of added SPH-d9) was recovered in the basolateral medium of (MM+SPH)-incubated cells, especially C23:0 Cer-d9 in (MM+SPH+C23:0)-enriched cells. In conclusion, present results indicate that MM enriched with (SPH+C23:0), such as found in postprandial micelles formed after milk SM ingestion, impact directly sphingolipids endogenous metabolism in enterocytes, resulting in the secretion of TG-rich particles enriched with C23:0 Cer.

Whole milk dairy foods and cardiometabolic health: dairy fat and beyond.

Bovine dairy milk is a nutrient-rich matrix, but consumption of full-fat dairy food varieties has been claimed historically to be associated with poorer cardiometabolic health, a notion often attributed to the saturated fat content. However, continued investigation that includes observational studies and randomized controlled trials (RCTs) provide evidence that favorably supports full-fat dairy foods and their bioactive components on cardiometabolic health. This review addresses this controversy by examining the evidence surrounding full-fat dairy foods and their implications for human health. Dairy foods are heterogeneous, not just in their fat content but also in other compositional aspects within and between fermented (e.g., yogurt, cheese) and nonfermented products (e.g., milk) that could differentially influence cardiometabolic health. Drawing from complementary lines of evidence from epidemiological studies and RCTs, this review describes the health effects of dairy foods regarding their fat content, as well as their polar lipids that are concentrated in the milk fat globule fraction. Observational studies have limitedly supported the consumption of full-fat dairy to protect against cardiometabolic disorders. However, this framework has been disputed by RCTs indicating that dairy foods, regardless of their fat content or fermentation, are not detrimental to cardiometabolic health and may instead alleviate certain cardiometabolic risk factors. As dietary recommendations evolve, which currently indicate to avoid full-fat dairy foods, it is essential to consider the totality of evidence, especially from RCTs, while also recognizing that investigation is needed to evaluate the complexity of dairy foods within diverse dietary patterns and their impacts on cardiometabolic health.

Multifunctional dietary interventions, low-grade inflammation and cardiometabolic profile: a scoping review.

Background: Growing evidence highlights the significant impact of diet to modify low-grade inflammation closely linked to cardiometabolic profile. Multifunctionnal diets, combining several compounds have been shown to beneficially impact metabolic parameters. Objective: This study synthesizes the knowledge on the impact of RCTs combining dietary multifunctional compounds on low-grade inflammation in humans. We investigate whether the effects of dietary multifunctional interventions on inflammatory markers were parallel to alterations of cardiometabolic parameters. Methodology: We considered both the integrated dietary interventions (ID, i.e. global diets such as Mediterranean, Nordic…) and the dietary interventions based on selected bioactive mix (BM) compounds, in healthy individuals and those at cardiometabolic risk. Out of 221 screened publications, we selected 27 studies: 11 for BM (polyphenols and/or omega-3 fatty acids and/or antioxidants and/or dietary fiber) and 16 for ID (Mediterranean, paleo, Nordic, Dietary Approaches to Stop Hypertension (DASH) diet…). Results: ID studies reflected significant improvements in inflammatory markers (CRP, IL-6, IL-10, IL-1b), concomitantly with beneficial changes in metabolic parameters. In BM studies, pronounced effects on low-grade inflammatory markers were observed, while improvements in metabolic parameters were not consistent. Both types of studies suggested a favorable impact on oxidative stress, a factor closely linked to the inflammatory profile. Conclusion: Our findings showed that multifunctional RCT diets have differential role in managing low-grade inflammation and cardiometabolic health, with a large heterogeneity in explored inflammatory markers. Further research is imperative to elucidate the link between low-grade inflammation and other cardiometabolic risk factors, such as intestinal inflammation or postprandial inflammatory dynamics, aiming to attain a comprehensive understanding of the mechanisms involved in these processes. These future investigations not only have the potential to deepen our insights into the connections among these elements but also pave the way for significant advancements in the prevention and management of conditions related to the cardiovascular and metabolic systems.

Postprandial lipid and vascular responses following consumption of a commercially-relevant interesterified palmitic acid-rich spread in comparison to functionally-equivalent non-interesterified spread and spreadable butter: a randomised controlled trial in healthy adults.

Background: Interesterification is an industrial processing technique used widely where hard fats are essential for functionality and consumer acceptability, e.g. margarines and lower fat spreads. Objective: The aim of this study was to compare acute cardiovascular effects of functionally equivalent spreads (similar solid fat content) made with interesterified (IE) or non-IE palm-based fats, or spreadable butter. Methods: A randomised, controlled, 4-armed crossover, double-blind study (25 men, 25 women; 35-75 years; healthy; mean BMI 24.5, SD 3.8), compared effects of mixed nutrient meals containing 50 g fat from functionally equivalent products [IE spread, non-IE spread and spreadable butter (SB), with rapeseed oil (RO) as a reference treatment: with 16.7%, 27.9%, 19.3% and 4% palmitic acid, respectively] on 8 h postprandial changes in plasma triacylglycerol (TAG) and endothelial dysfunction (flow-mediated dilatation; FMD). Circulating reactive oxygen species (estimated using a neutrophil oxidative burst assay), glucose, insulin, NEFA, lipoprotein particle profiles, inflammatory markers (glycoprotein acetylation (Glyc-A) and IL-6), and biomarkers of endotoxemia were measured. Results: Postprandial plasma TAG concentrations after test meals were similar. However following RO versus the 3 spreads, there were significantly higher postprandial apolipoprotein B concentrations, and small HDL and LDL particle concentrations, and lower postprandial extra-large, large, and medium HDL particle concentrations, as well as smaller average HDL and LDL particle sizes. There were no differences following IE compared to the other spreads. Postprandial FMD% did not decrease after high-fat test meals, and there were no differences between treatments. Postprandial serum IL-6 increased similarly after test meals, but RO provoked a greater increase in postprandial concentrations of glycoprotein acetyls (GlycA), as well as 8 h sCD14, an endotoxemia marker. All other postprandial outcomes were not different between treatments. Conclusions: In healthy adults, a commercially-available IE-based spread did not evoke a different postprandial triacylglycerol, lipoprotein subclass, oxidative stress, inflammatory or endotoxemic response to functionally-equivalent, but compositionally-distinct alternative spreads. Clinical trial registry number: NCT03438084 (https://ClinicalTrials.gov).

Inhibition of intestinal FXR activity as a possible mechanism for the beneficial effects of a probiotic mix supplementation on lipid metabolism alterations and weight gain in mice fed a high fat diet.

Supplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix of Bifidobacterium animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 on high-fat (HF) diet -induced metabolic disease in mice. Supplementation with the probiotic mix in HF diet-fed mice (HF-Pr2) reduced weight and fat mass gains, decreased hepatic lipid accumulation, and lowered plasma triglyceride peak during an oral lipid tolerance test. At the molecular level, the probiotic mix protected against HF-induced rise in mRNA levels of genes related to lipid uptake, metabolism, and storage in the liver and white adipose tissues, and strongly decreased mRNA levels of genes related to inflammation in the white adipose tissue and to oxidative stress in the liver. Regarding intestinal homeostasis, the probiotic mix did not prevent HF-induced gut permeability but slightly modified microbiota composition without correcting the dysbiosis induced by the HF diet. Probiotic supplementation also modified the cecal bile acid (BA) profile, leading to an increase in the Farnesoid-X-Receptor (FXR) antagonist/agonist ratio between BA species. In agreement, HF-Pr2 mice exhibited a strong inhibition of FXR signaling pathway in the ileum, which was associated with lipid metabolism protection. This is consistent with recent reports proposing that inhibition of intestinal FXR activity could be a potent mechanism to overcome metabolic disorders. Altogether, our results demonstrate that the probiotic mix evaluated, when administered preventively to HF diet-fed mice could limit obesity and associated lipid metabolism disorders, likely through the inhibition of FXR signaling in the intestinal tract.

Validation of Knock-Out Caco-2 TC7 Cells as Models of Enterocytes of Patients with Familial Genetic Hypobetalipoproteinemias.

Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in MTTP and SAR1B genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (-57.0 ± 2.6% to -83.9 ± 1.6%) and cholesterol (-35.3 ± 4.4% to -60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (-41.5 ± 3.7% to -97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism.

Soy Lecithin in High-Fat Diets Exerts Dual Effects on Adipose Tissue Versus Ileum.

SCOPE: Lipopolysaccharides and their transporters, LBP and sCD14, are involved in systemic inflammation following a high-fat diet. Natural emulsifiers such as soy lecithin, rich in soybean polar lipids (SPL), are often used by the food industry but little is known about effects of associating SPL with different oils. METHODS AND RESULTS: Thus, this study investigates the effects of 4 weeks feeding of palm (P) or rapeseed (R) oil-enriched diets with or without SPL in mice, on white adipose tissue (WAT) inflammation, on ileum permeability, and on microbiota composition. When SPL are associated with rapeseed oil, a greater gene expression of leptin and inflammation in WAT is observed compared to P-SPL. In ileum, R-SPL group results in a lower expression of TLR4, IAP that detoxify bacterial LPS and tight junction proteins than R group. In turn, the gene expression of Reg3ß and Reg3γ, which have antimicrobial activity, is higher in ileum of R-SPL group than in R group. SPL in rapeseed oil increases specific bacterial species belonging to Lachnospiraceae, Alistipes, and Bacteroidales. CONCLUSION: The incorporation of SPL in a diet with rapeseed oil exerts differential effect on WAT and ileum, with respectively an inflammation of WAT and an antimicrobial activity in ileum, associated with specific microbiota changes.

A meal rich in palm oil or butter modifies the sphingolipid profile of postprandial triglyceride-rich lipoproteins from type 2 diabetic women.

Elevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and some sphingolipids (SP) have been validated as potent predictive biomarkers of cardiovascular disease occurrence. The main objectives of the present study were to characterize the plasma SP profile in fasting T2D patients and to determine whether SP are modified in postprandial TGRL from these patients compared to fasting TGRL. In a randomized parallel-group study, 30 T2D women ingested a breakfast including 20g lipids from either hazelnut cocoa palm oil-rich spread (Palm Nut) or Butter. Plasma was collected and TGRL were isolated by ultracentrifugation at fasting and 4h after the meal. Fasting samples of 6 control subjects from another cohort were analyzed for comparison. SP were analyzed by tandem mass spectrometry. Plasma from fasting T2D patients had higher ceramide (Cer) and ganglioside GM3 concentrations, and lower concentrations of sphingosylphosphorylcholine vs healthy subjects. In postprandial TGRL from T2D patients compared to those in the fasting state, Cer concentrations and especially C16:0, C24:1 and C24:0 molecular species, increased after the Palm Nut or Butter breakfast. A positive correlation was observed in the Palm Nut group between changes (Δ4h-fasting) of summed C16:0+C22:0+C24:1+C24:0 Cer concentrations in TGRL, and changes in plasma TG, TGRL-TG and TGRL-C16:0 concentrations. Altogether in T2D, the altered profile of plasma SP and the increased Cer concentrations in postprandial TGRL could contribute to the increased atherogenicity of TGRL.

The digestion of diacylglycerol isomers by gastric and pancreatic lipases and its impact on the metabolic pathways for TAG re-synthesis in enterocytes.

The specific activities of gastric and pancreatic lipases were measured using triacylglycerols (TAG) from rapeseed oil, purified 1,3-sn-DAG and 1,2(2,3)-sn-DAG produced from this oil, as well as a rapeseed oil enriched with 40% w/w DAG (DAGOIL). Gastric lipase was more active on 1,3-sn-DAG than on 1,2(2,3)-sn-DAG and TAG, whereas pancreatic lipase displayed a reverse selectivity with a higher activity on TAG than on DAG taken as initial substrates. However, in both cases, the highest activities were displayed on DAGOIL. These findings show that DAG mixed with TAG, such as in the course of digestion, is a better substrate for lipases than TAG. The same rapeseed oil acylglycerols were used to investigate intestinal fat absorption in rats with mesenteric lymph duct cannulation. The levels of TAG synthesized in the intestine and total fatty acid concentration in lymph were not different when the rats were fed identical amounts of rapeseed oil TAG, 1,2(2,3)-sn-DAG, 1,3-sn-DAG or DAGOIL. Since the lipolysis of 1,3-sn-DAG by digestive lipases leads to glycerol and not 2-sn-monoacylglycerol (2-sn-MAG) like TAG lipolysis, these results suggest that the re-synthesis of TAG in the enterocytes can entirely occur through the "glycerol-3-phosphate (G3P)" pathway, with the same efficiency as the 2-sn-MAG pathway predominantly involved in the intestinal fat absorption. These findings shed new light on the role played by DAG as intermediate lipolysis products. Depending on their structure, 1,2(2,3)-sn-DAG versus 1,3-sn-DAG, DAG may control the pathway (2-sn-MAG or G3P) by which TAG are re-synthesized in the enterocytes.

Role of circulating sphingolipids in lipid metabolism: Why dietary lipids matter.

Sphingolipids are structural components of cell membranes and lipoproteins but also act as signaling molecules in many pathophysiological processes. Although sphingolipids comprise a small part of the plasma lipidome, some plasma sphingolipids are recognized as implicated in the development of metabolic diseases and cardiovascular diseases. Plasma sphingolipids are mostly carried out into lipoproteins and may modulate their functional properties. Lipids ingested from the diet contribute to the plasma lipid pool besides lipids produced by the liver and released from the adipose tissue. Depending on their source, quality and quantity, dietary lipids may modulate sphingolipids both in plasma and lipoproteins. A few human dietary intervention studies investigated the impact of dietary lipids on circulating sphingolipids and lipid-related cardiovascular risk markers. On the one hand, dietary saturated fatty acids, mainly palmitic acid, may increase ceramide concentrations in plasma, triglyceride-rich lipoproteins and HDL. On the other hand, milk polar lipids may decrease some molecular species of sphingomyelins and ceramides in plasma and intestine-derived chylomicrons. Altogether, different dietary fatty acids and lipid species can modulate circulating sphingolipids vehicled by postprandial lipoproteins, which should be part of future nutritional strategies for prevention of cardiovascular diseases.

A Mix of Dietary Fibres Changes Interorgan Nutrients Exchanges and Muscle-Adipose Energy Handling in Overfed Mini-Pigs.

This study evaluates the capacity of a bread enriched with fermentable dietary fibres to modulate the metabolism and nutrients handling between tissues, gut and peripheral, in a context of overfeeding. Net fluxes of glucose, lactate, urea, short chain fatty acids (SCFA), and amino acids were recorded in control and overfed female mini-pigs supplemented or not with fibre-enriched bread. SCFA in fecal water and gene expressions, but not protein levels or metabolic fluxes, were measured in muscle, adipose tissue, and intestine. Fibre supplementation increased the potential for fatty acid oxidation and mitochondrial activity in muscle (acox, ucp2, sdha and cpt1-m, p < 0.05) as well as main regulatory transcription factors of metabolic activity such as pparα, pgc-1α and nrf2. All these features were associated with a reduced muscle fibre cross sectional area, resembling to controls (i.e., lean phenotype). SCFA may be direct inducers of these cross-talk alterations, as their feces content (+52%, p = 0.05) was increased in fibre-supplemented mini-pigs. The SCFA effects could be mediated at the gut level by an increased production of incretins (increased gcg mRNA, p < 0.05) and an up-regulation of SCFA receptors (increased gpr41 mRNA, p < 0.01). Hence, consumption of supplemented bread with fermentable fibres can be an appropriate strategy to activate muscle energy catabolism and limit the establishment of an obese phenotype.

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

BACKGROUNDHigh 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.METHODSIn 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.RESULTSMilk 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.CONCLUSIONMilk 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 REGISTRATIONClinicalTrials.gov, NCT02099032, NCT02146339.FUNDINGANR-11-ALID-007-01; PHRCI-2014: VALOBAB, no. 14-007; CNIEL; GLN 2018-11-07; HCL (sponsor).

Impact of Rapeseed and Soy Lecithin on Postprandial Lipid Metabolism, Bile Acid Profile, and Gut Bacteria in Mice.

SCOPE: Synthetic emulsifiers have recently been shown to promote metabolic syndrome and considerably alter gut microbiota. Yet, data are lacking regarding the effects of natural emulsifiers, such as plant lecithins rich in essential α-linolenic acid (ALA), on gut and metabolic health. METHODS AND RESULTS: For 5 days, male Swiss mice are fed diets containing similar amounts of ALA and 0, 1, 3, or 10% rapeseed lecithin (RL) or 10% soy lecithin (SL). Following an overnight fast, they are force-fed the same oil mixture and euthanized after 90 minutes. The consumption of lecithin significantly increased fecal levels of the Clostridium leptum group (p = 0.0004), regardless of origin or dose, without altering hepatic or intestinal expression of genes of lipid metabolism. 10%-RL increased ALA abundance in plasma triacylglycerols at 90 minutes, reduced cecal bile acid hydrophobicity, and increased their sulfatation, as demonstrated by the increased hepatic RNA expression of Sult2a1 (p = 0.037) and cecal cholic acid-7 sulfate (CA-7S) concentration (p = 0.05) versus 0%-lecithin. CONCLUSION: After only 5 days, nutritional doses of RL and SL modified gut bacteria in mice, by specifically increasing C. leptum group. RL also increased postprandial ALA abundance and induced beneficial modifications of the bile acid profile. ALA-rich lecithins, especially RL, may then appear as promising natural emulsifiers.

Rapeseed Lecithin Increases Lymphatic Lipid Output and α-Linolenic Acid Bioavailability in Rats.

BACKGROUND: Soybean lecithin, a plant-based emulsifier widely used in food, is capable of modulating postprandial lipid metabolism. With arising concerns of sustainability, alternative sources of vegetal lecithin are urgently needed, and their metabolic effects must be characterized. OBJECTIVES: We evaluated the impact of increasing doses of rapeseed lecithin (RL), rich in essential α-linolenic acid (ALA), on postprandial lipid metabolism and ALA bioavailability in lymph-cannulated rats. METHODS: Male Wistar rats (8 weeks old) undergoing a mesenteric lymph duct cannulation were intragastrically administered 1 g of an oil mixture containing 4% ALA and 0, 1, 3, 10, or 30% RL (5 groups). Lymph fractions were collected for 6 h. Lymph lipids and chylomicrons (CMs) were characterized. The expression of genes implicated in intestinal lipid metabolism was determined in the duodenum at 6 h. Data was analyzed using either sigmoidal or linear mixed-effects models, or one-way ANOVA, where appropriate. RESULTS: RL dose-dependently increased the lymphatic recovery (AUC) of total lipids (1100 µg/mL·h per additional RL%; P = 0.010) and ALA (50 µg/mL·h per additional RL%; P = 0.0076). RL induced a faster appearance of ALA in lymph, as evidenced by the exponential decrease of the rate of appearance of ALA with RL (R2 = 0.26; P = 0.0064). Although the number of CMs was unaffected by RL, CM diameter was increased in the 30%-RL group, compared to the control group (0% RL), by 86% at 3-4 h (P = 0.065) and by 81% at 4-6 h (P = 0.0002) following administration. This increase was positively correlated with the duodenal mRNA expression of microsomal triglyceride transfer protein (Mttp; ρ= 0.63; P = 0.0052). The expression of Mttp and secretion-associated, ras-related GTPase 1 gene homolog B (Sar1b, CM secretion), carnitine palmitoyltransferase IA (Cpt1a) and acyl-coenzyme A oxidase 1 (Acox1, beta-oxidation), and fatty acid desaturase 2 (Fads2, bioconversion of ALA into long-chain n-3 PUFAs) were, respectively, 49%, 29%, 74%, 48%, and 55% higher in the 30%-RL group vs. the control group (P < 0.05). CONCLUSIONS: In rats, RL enhanced lymphatic lipid output, as well as the rate of appearance of ALA, which may promote its subsequent bioavailability and metabolic fate.

Dietary lipids and cardiometabolic health: a new vision of structure-activity relationship.

PURPOSE OF REVIEW: The impact of dietary lipids on cardiometabolic health was mainly studied considering their fatty acid composition. This review aims to present the recent change in paradigm whereby the food matrix, the molecular and supramolecular structures of dietary lipids modulate their digestive fate and cardiometabolic impact. RECENT FINDINGS: Epidemiological studies have reported that the metabolic impact of full-fat dairy products is better than predictable upon saturated fatty acid richness. Milk polar lipid supplementation reduced adiposity and inflammation in rodents by modulating gut microbiota and barrier, and decreased lipid markers of cardiovascular disease risk in humans by lowering cholesterol absorption. The metabolic importance of the structure of lipid molecules carrying omega-3 (molecular carrier) has also been documented. Plant lipids exhibit specific assemblies, membrane and molecular structures with potential health benefits. Lipid emulsifiers used to stabilize fats in processed foods are not mere bystanders of lipid effects and can induce both beneficial and adverse health effects. SUMMARY: These findings open new clinical research questions aiming to further characterize the cardiometabolic fate of lipids, from digestion to bioactive metabolites, according to the food source or molecular carrier. This should be useful to elaborate food formulations for target populations and personalized dietary recommendations.

Postprandial Triglyceride-Rich Lipoproteins from Type 2 Diabetic Women Stimulate Platelet Activation Regardless of the Fat Source in the Meal.

SCOPE: The aim of this study is to examine whether postprandial (PP) triglyceride-rich lipoproteins (TGRL) secreted after a moderate fat intake would activate platelets differently according to their fatty acid (FA) composition. METHODS AND RESULTS: In a parallel single-blind randomized trial, 30 women with type 2 diabetes are assigned a breakfast containing 20 g lipids from butter versus hazelnut-cocoa spread (HCS) rich in palm oil. Blood samples are collected at fasting and 4 h PP. FA composition of fasting and PP TGRL and their effects on the activation of platelets from healthy blood donors are assessed. Both breakfasts similarly increase plasma ApoB-48, plasma, and TGRL triglycerides (p < 0.05). TGRL mean diameter increases after both breakfasts and is greater after the butter breakfast. Both breakfasts are rich in palmitic acid, and the HCS breakfast contains 45% oleic acid. TGRL FA composition reflects the dietary FA composition. Pre-incubation of platelets with fasting and PP TGRL increases collagen-stimulated aggregation (p < 0.01 vs control). Fasting and PP TGRL similarly increase agonist-induced thromboxane B2 concentrations, and this effect is concentration-dependent for PP TGRL. CONCLUSION: PP TGRL from type 2 diabetic women after a palm-oil spread versus butter-based mixed meal induce similar acute in vitro platelet activation.

Human milk pasteurisation reduces pre-lipolysis but not digestive lipolysis and moderately decreases intestinal lipid uptake in a combination of preterm infant in vitro models.

Donor human milk, pasteurised for safety reasons, is the first alternative for feeding preterm infants when mothers' own milk is unavailable. Breastmilk pasteurisation impact on lipid digestion and absorption was evaluated by a static in vitro digestion model for preterm infants coupled with intestinal absorption using Caco-2/TC7 cells. Lipid absorption was quantified by digital image analysis of lipid droplets, by measurement of basolateral triglyceride concentration and by analysing the expression of major genes involved. After in vitro digestion, lipolysis extent was 13% lower in pasteurised human milk (PHM) than in raw human milk (RHM). In Caco-2/TC7 cells, the number of lipid droplets was identical for both milk types, while the mean droplet area was 17% smaller with PHM. Altogether, pasteurisation decreased the pre-lipolysis of human milk. This initial difference in free fatty acid amount was only partially buffered by the subsequent processes of in vitro digestion and cellular lipid absorption.

Postprandial Endotoxin Transporters LBP and sCD14 Differ in Obese vs. Overweight and Normal Weight Men during Fat-Rich Meal Digestion.

Circulating levels of lipopolysaccharide-binding protein (LBP) and soluble cluster of differentiation 14 (sCD14) are recognized as clinical markers of endotoxemia. In obese men, postprandial endotoxemia is modulated by the amount of fat ingested, being higher compared to normal-weight (NW) subjects. Relative variations of LBP/sCD14 ratio in response to overfeeding are also considered important in the inflammation set-up, as measured through IL-6 concentration. We tested the hypothesis that postprandial LBP and sCD14 circulating concentrations differed in obese vs. overweight and NW men after a fat-rich meal. We thus analyzed the postprandial kinetics of LBP and sCD14 in the context of two clinical trials involving postprandial tests in normal-, over-weight and obese men. In the first clinical trial eight NW and 8 obese men ingested breakfasts containing 10 vs. 40 g of fat. In the second clinical trial, 18 healthy men were overfed during 8 weeks. sCD14, LBP and Il-6 were measured in all subjects during 5 h after test meal. Obese men presented a higher fasting and postprandial LBP concentration in plasma than NW men regardless of fat load, while postprandial sCD14 was similar in both groups. Irrespective of the overfeeding treatment, we observed postprandial increase of sCD14 and decrease of LBP before and after OF. In obese individuals receiving a 10 g fat load, whereas IL-6 increased 5h after meal, LBP and sCD14 did not increase. No direct association between the postprandial kinetics of endotoxemia markers sCD14 and LBP and of inflammation in obese men was observed in this study.

Probiotic from human breast milk, Lactobacillus fermentum, promotes growth in animal model of chronic malnutrition.

BACKGROUND: Chronic undernutrition leads to growth hormone resistance and poor growth in children, which has been shown to be modulated by microbiota. We studied whether Lactobacillus fermentum CECT5716 (Lf CECT5716), isolated from mother's breast milk, could promote juvenile growth through the modulation of lipid absorption in a model of starvation. METHODS: Germ-free (GF) Drosophila melanogaster larvae were inoculated with Lf CECT5716 in conditions of undernutrition with and without infant formula. The impact of Lf CECT5716 on larval growth was assessed 7 days after egg laying (AED) by measuring the larval size and on maturation by measuring the emergence of pupae during 21 days AED. For lipid absorption test, Caco2/TC7 intestinal cells were incubated with Lf CECT5716 and challenged with mixed lipid micelles. RESULTS: The mono-associated larvae with Lf CECT5716 were significantly longer than GF larvae (3.7 vs 2.5 mm; p < 0.0001). The effect was maintained when Lf CECT5716 was added to the infant formula. The maturation time of larvae was accelerated by Lf CECT5716 (12 vs 13.2 days; p = 0.01). Lf CECT5716 did not have significant impact on lipid absorption in Caco2/TC7 cells. CONCLUSIONS: Lf CECT5716 is a growth-promoting strain upon undernutrition in Drosophila, with a maintained effect when added to an infant formula but without effect on lipid absorption in vitro.

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

OBJECTIVE: To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health. DESIGN: A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients. RESULTS: Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut. CONCLUSION: The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota. TRIAL REGISTRATION NUMBER: NCT02099032 and NCT02146339; Results.