Plant-based proteins are promising alternatives to animal proteins for supporting muscle synthesis and preventing sarcopenia. This study examined whether protein digestates (PDs) from pea and fava bean isolates modulate intestinal Fibroblast Growth Factor 19 (FGF19), a hormone central to energy and muscle mass regulation. Human HT29 cells were exposed to PDs, GW4064 (FXR agonist), or rosiglitazone (PPAR gamma agonist). FGF19 secretion was assessed by ELISA, gene expression by RT-qPCR, and FXR protein by Western-blot. At 6 h, PDs alone had no effect on FGF19 expression but potentiated GW4064 activity by lowering its EC50. At 24 h, PDs modestly increased FGF19 and continued to potentiate GW4064 activity. Rosiglitazone + GW4064 markedly increased FGF19 and FXR expression, an effect abolished by GW9662 (PPAR gamma inhibitor), confirming PPAR gamma involvement. GW9662 also suppressed FGF19 induction by PDs + GW4064. Thus, PPAR gamma may regulate the FXR-FGF19 axis in enterocytes. Both PDs and rosiglitazone enhance FXR-mediated FGF19, with PDs partly acting through PPAR gamma. Pea and fava bean proteins may offer nutritional strategies for metabolic health and sarcopenia prevention.

Dairy products are major dietary sources of B vitamins. However, the impact of cow diet and dairy processing techniques on B vitamin concentrations remains unclear. This study investigated the effects of diet composition on B-vitamin content in raw milk and, in yogurt, and Cantal-type cheese produced therefrom. Forty Holstein and Montbéliarde-breed cows were assigned to either a grass-based agroecological system or a corn-based intensive system for 19 weeks. Vitamins B1, B2, B5, and B6 were quantified by liquid chromatography, and B9 and B12 by chemiluminescence. Milk from the agroecological system contained higher vitamin B2, and lower vitamin B5 concentrations than milk from the intensive system. This same pattern was also observed in cheese, but not in yogurt, showing impacts of technological processing. Adding probiotics into yogurts increased pyridoxal (B6) concentration. This study highlighted diet-related differences in B vitamin concentrations in raw milk, and these differences transferred to cheese but not to yogurt.

Objectives: Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, increasing evidence points to a pivotal role of the gut. Aiming to clarify whether metformin-induced changes in the intestinal tract directly contribute to metabolic improvement, we evaluated the effects of escalating doses (from 50 to 200 mg/kg/day) of metformin orally administered for 4 weeks in mice made glucose intolerant by ten weeks of high fat high sucrose diet. Methods: Several intestinal parameters were studied, including caecal microbiota composition and bile acids profile, ileal FXR signaling, abundance of GLP1-producing cells and goblet cells and blood metabolome. Results: Metformin restored glucose tolerance, fasting insulinemia and HOMA-IR index in a dose-dependent manner. Only a subset of gut-related effects, including mucus production and GLP-1 expression, exhibited a parallel dose–response relationship, suggesting a possible contribution to the observed metabolic improvements. In contrast, other changes, including ileal Fxr-Fgf15 inhibition and hepatic ceramide reduction did not scale with dose, suggesting they are not the main drivers of metformin dose-dependent effects on glycemic control. We also pointed out marked differential sensitivity of gut bacteria to metformin supporting complex interactions of the drug with the microbial ecosystem. Conclusion: Finally, metformin enhanced the proliferation of intestinal epithelium, resulting in increased length of ileal villi. Altogether, this study offers new insights into the metformin mechanism of action and revealed potential novel microbial biomarkers and targets for enhancing its therapeutic efficacy.

Most current dietary guidelines for the prevention of cardiovascular diseases (CVD) recommend the consumption of low-fat dairy in place of regular-fat dairy foods, one of the main sources of dietary saturated fatty acids (SFAs). Here, we summarize the data presented and discussions held-relating to the validity of such recommendations-between a panel of international nutrition research experts at a high-level closed workshop on "Saturated Fat in Dairy and Cardiovascular Diseases," which took place in Amsterdam on 15-16 April, 2024. The most recent evidence indicates that overall, consumption of milk, yogurt and cheese, irrespective of fat content, is neutrally associated with CVD risk. There is also no evidence yet from randomized controlled trials that consumption of regular-fat milk, yogurt, and cheese has different effects on a broad array of cardiometabolic risk factors when compared with consumption of low-fat milk, yogurt, and cheese. Thus, the body of evidence does not support differentiation between regular-fat and low-fat dairy foods in dietary guidelines for both adults and children. Strategies focusing primarily on reduction of energy-dense, nutrient-poor foods, the main source of SFAs in Western diets, rather than on the fat content of dairy foods, are more likely to benefit the population's cardiovascular health. Future research is needed to understand better the place of regular-fat and low-fat dairy foods within healthy eating patterns.

Lipids are essential for child development. Nutritional recommendations are numerous, evolving over time and are often based on expert opinions more than evidence-based medicine. The objective of this review is to critically analyse the evolution of current nutritional recommendations, identify existing knowledge gaps and propose avenues for improvement to optimise infant nutrition and development. A narrative literature review on Pubmed, EMBASE and Cochrane databases (2001-22) was conducted with the keywords: 'alpha-linolenic acid, arachidonic acid, children, cholesterol, docosahexaenoic acid, eicosapentaenoic acid, guidelines, infant, long-chain (LC) PUFA, linoleic acid, lipids and dietary intakes, newborn, palmitic acid and toddler'. Among 861 articles identified, 133 were selected. The main current recommendations are issued by the French Agency for Food Safety (AFSSA), French Agency for Food, Environmental and Occupational Health and Safety (ANSES) and the Food and Agriculture Organization and World Health Organization (FAO-WHO). In infants from 0 to 3 years of age the main challenge is to increase lipid intake while maintaining an optimal omega 6/omega 3 ratio. Current recommendations are focused on polyunsaturated fatty acids, emphasising the intake of linoleic, eicosapentaenoic and docosahexaenoic acids without any specific recommendation for arachidonic acid before the age of 6 months. Points of interest, but without any recommendation, are the incorporation of milk fat, cholesterol, monounsaturated fatty acids, and saturated fatty acids for infants under 6 months. In conclusion, this article identifies knowledge gaps regarding the structural aspect of lipids and the integration of new categories of lipids in future recommendations to promote the quality of infant formulas.

The health impact of dairy products is debated due to their high saturated fatty acid (SFA) content. Emerging evidence suggests that dairy products intake may reduce cardiovascular disease risk, despite their SFA-rich lipids, leading to the “dairy food matrix” concept. Nevertheless, the impact of lipid and SFA intake from whole dairy sources on cardio-metabolic health remains poorly understood. This study investigated the cross-sectional association of SFA intake from various types of dairy products and dairy fat sources with cardio-metabolic outcomes. Data from 1619 participants of the STANISLAS cohort, who underwent extensive metabolic and cardiovascular phenotyping and completed a 133-item food frequency questionnaire covering dairy products and other dairy fat sources, were used. Associations of total dietary lipid, total dietary SFA, and SFA intakes from dairy products and dairy fat sources with metabolic outcomes (metabolic syndrome, hyperlipidemia, type 2 diabetes, prediabetes) and subclinical cardiovascular damages (i.e., arterial stiffness, atherosclerosis, left ventricular mass, diastolic dysfunction) were assessed using mixed models. Median [interquartile range] lipid consumption via dairy products and dairy fat sources was 23 [15, 34] g/day. Higher total dietary lipid intake was associated with lower arterial stiffness (exp(β) [95

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 other compositional aspects within and between fermented (e.g., yogurt and cheese) and non-fermented 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 its fat content, as well as its 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.

BackgroundGrowing 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.ObjectiveThis 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.MethodologyWe 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…).ResultsID 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.ConclusionOur 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.

Background: Interesterification is an industrial processing technique used to create hard fats where this is essential for functionality and consumer acceptability, e.g. margarines and lower fat spreads.

SCOPE:Consumption of high-fat meals is associated with increased endotoxemia, inflammation, and atherogenic profiles, with repeated postprandial responses suggested as contributors to chronically elevated risk factors. However, effects of lipid solid versus liquid state specifically have not been investigated. METHODS AND RESULTS:This exploratory randomized crossover study tests the impact of lipid crystallinity on plasma levels of endotoxin transporters (lipopolysaccharide [LPS] binding protein [LBP] and soluble cluster of differentiation 14 [sCD14]) and select proinflammatory and atherogenic markers (tumor necrosis factor-alpha [TNF-α], C-reactive protein [CRP], interleukin-1-beta [IL-1β], interferon-gamma [IFN-γ], interleukin-6 [IL-6], soluble intercellular adhesion molecule [sICAM], soluble vascular cell adhesion molecule [sVCAM], monocyte chemoattractant protein-1 [MCP-1/CCL2], plasminogen activator inhibitor-1 [PAI-1], and fibrinogen). Fasted healthy men (n = 14, 28 ± 5.5 years, 24.1 ± 2.6 kg m-2) consumed two 50 g palm stearin oil-in-water emulsions tempered to contain either liquid or crystalline lipid droplets at 37 °C on separate occasions with blood sampling at 0, 2-, 4-, and 6-h post-meal. Timepoint data, area under the curve, and peak concentration values are compared. Overall, no treatment effects are seen (p > 0.05). There are significant effects of time, with values decreasing from baseline, for TNF-α, MCP-1/CCL2, PAI-1, and fibrinogen (p < 0.05). CONCLUSION:Responder analysis pointed to differential treatment effects associated with some participant baseline characteristics but, overall, palm-stearin emulsion droplet crystallinity does not acutely affect plasma endotoxin transporters nor select inflammatory and atherogenic markers.

The development of cardiometabolic (CM) diseases is associated with chronic low-grade inflammation, partly linked to alterations of the gut microbiota (GM) and reduced intestinal integrity. The SINFONI project investigates a multifunctional (MF) nutritional strategy’s impact combining different bioactive compounds on inflammation, GM modulation and CM profile. In this randomized crossover-controlled study, 30 subjects at CM-risk consumed MF cereal-products, enriched with polyphenols, fibers, slowly-digestible starch, omega-3 fatty acids or Control cereal-products (without bioactive compounds) for 2 months. Metabolic endotoxemia (lipopolysaccharide (LPS), lipopolysaccharide-binding protein over soluble cluster of differentiation-14 (LBP/sCD14), systemic inflammation and cardiovascular risk markers, intestinal inflammation, CM profile and response to a one-week fructose supplementation, were assessed at fasting and post mixed-meal. GM composition and metabolomic analysis were conducted. Mixed linear models were employed, integrating time (pre/post), treatment (MF/control), and sequence/period. Compared to control, MF intervention reduced intestinal inflammation (fecal calprotectin, p = 0.007) and endotoxemia (fasting LPS, p < 0.05), without alteration of systemic inflammation. MF decreased serum branched-chain amino acids compared to control (p < 0.05) and increased B.ovatus, B.uniformis, A.butyriciproducens and unclassified Christensenellaceae.CAG-74 (p < 0.05). CM markers were unchanged. A 2-month dietary intervention combining multiple bioactive compounds improved intestinal inflammation and induced GM modulation. Such strategy appears as an effective strategy to target low-grade inflammation through multi-target approach.

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 the uptake and metabolism of SPH and/or tricosanoic acid (C23:0), the main FA of milk SM, as well as lipid secretion in Caco-2/TC7 cells cultured on semipermeable inserts. 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 coaddition of C23:0 in SPHenriched 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, directly impacts sphingolipid endogenous metabolism in enterocytes, resulting in the secretion of TG -rich particles enriched with C23:0 Cer.

ScopeLipopolysaccharides 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 resultsThus, 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 Reg3β 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.ConclusionThe 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.

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.

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.

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.