Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation.

International audienceMetabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly during the digestion of lipids. The aim of the present review is to highlight recently gained knowledge regarding the links between high fat diets, lipid digestion, intestinal microbiota and metabolic endotoxemia & inflammation

Impact de la structure de la matière grasse sur l'absorption et le devenir métabolique des lipides et des endotoxines chez l'Homme normo-pondéré ou obèse

The alteration of postprandial lipid metabolism and associated chronic inflammation emerge as major elements in the obesity pathophysiology. The involvement of the intestinal absorption of endotoxin from microbiota during lipid digestion was recently highlighted. However, the modulation of these phenomena by different amounts of differently structured lipids remains poorly characterized, especially in obese people. We developed a cross-over randomized clinical study to explore in normal weight and obese subjects the consequences of fat digestion, consumed either spread on bread in different amounts (10 g or 40 g) or finely emulsified (40 g), on postprandial metabolism of lipids and endotoxins. We have demonstrated that the increase in plasma chylomicrons, after increase in the amount of fat ingested, was earlier and greater in normal-weight than in obese subjects, with the secretion of larger chylomicrons after consumption of 40 g of spread fat. When 40 g of fat is emulsified, we show that it leads to an earlier and higher peak of chylomicron triglycerides, reflecting facilitated absorption of fat, and more significantly in obese subjects. We also show that emulsified fat results in higher β-oxidation of exogenous lipids over the day, with no difference in fecal excretion. Postprandial endotoxemia was also observed in response to different meals. The postprandial accumulation of endotoxins, present in chylomicrons, increases with the amount of spread fat ingested and it is correlated with the area under the curve of chylomicrons in obese subjects. In addition, the in vitro lipid absorption by Caco-2 cells was greater following incubation with lipolysis media of emulsions stabilized by caseinate than lecithin. Finally, a digestion test was conducted before and after gastric bypass surgery to identify whether a drastic reduction in lipid absorption altered metabolic endotoxemia. After surgery, patients are more exposed to endotoxins in the morning after emulsion consumption at breakfast. However, LBP, a proinflammatory protein transporting endotoxins, significantly decreases after surgery. Altogether, these studies demonstrate that in addition to the metabolic effects of dietary fat intake on lipemia and associated endotoxemia, the fat structure also plays an important role in the modulation of further fatty acid handling. Structuring of dietary lipids could thus be specifically adapted to optimize postprandial lipid metabolism, especially in obese people.L’altération du métabolisme postprandial des lipides et l’inflammation chronique associée apparaissent comme des éléments majeurs de la physiopathologie de l’obésité. L’implication de l’absorption intestinale d’endotoxines bactériennes du microbiote au cours de la digestion des lipides a été mise en évidence. Cependant la modulation de ces phénomènes par différentes quantités de lipides différemment structurés reste mal caractérisée, notamment chez les obèses. Nous avons mis en place un protocole clinique, en cross-over randomisé, visant à étudier chez des sujets normo-pondérés et obèses les conséquences de la digestion de matière grasse consommée, soit sous forme tartinée en différentes quantités (10 g ou 40 g), soit sous forme finement émulsionnée (40 g) sur le métabolisme postprandial des lipides et des endotoxines. Nous avons ainsi mis en évidence que l’augmentation plasmatique des chylomicrons, suite à une augmentation de la quantité de matière grasse ingérée, était plus précoce et plus importante chez les normo-pondérés que chez les sujets obèses, avec la sécrétion de plus gros chylomicrons suite à 40 g. Lorsque 40 g de matière grasse est émulsionnée, nous montrons qu’elle aboutit à un pic de triglycérides des chylomicrons plus précoce et plus élevé, reflétant une absorption facilitée des lipides, et de manière plus marquée chez l’obèse. Nous montrons aussi que cet état émulsionné aboutit à une β-oxydation plus élevée des lipides exogènes sur la journée, sans différence de perte fécale. Une endotoxémie postprandiale est également observée suite aux différents repas. L’accumulation postprandiale d’endotoxines, notamment présentes dans les chylomicrons, augmente avec la quantité de matière grasse tartinée en corrélation avec l’aire sous courbe des chylomicrons chez les obèses. En complément, l’absorption lipidique in vitro par des cellules Caco-2 était plus importante suite à l’incubation de milieux de lipolyse d’émulsions stabilisées par du caséinate que de la lécithine. Enfin, un test de digestion a été réalisé avant et après une chirurgie de by-pass gastrique pour identifier si une diminution drastique de l’absorption lipidique modifiait l’endotoxémie. Suite à l’opération, les patients sont davantage exposés aux endotoxines après la prise d’une émulsion au petit-déjeuner. En revanche, la LBP, protéine de transport des endotoxines proinflammatoire, diminue significativement à jeun et en postprandial suite à l’opération. L’ensemble de ces travaux démontrent qu’en plus des effets de la quantité de lipides ingérée sur la lipémie et l’absorption d’endotoxines associée, la structure de la matière grasse joue un rôle important dans la modulation du devenir métabolique des acides gras. La structuration des lipides alimentaires pourrait donc être spécifiquement adaptée afin d’optimiser le métabolisme lipidique postprandial, notamment chez des personnes obèses

Impact of fat structure on lipid and endotoxin absorption and metabolic fate in humans

L’altération du métabolisme postprandial des lipides et l’inflammation chronique associée apparaissent comme des éléments majeurs de la physiopathologie de l’obésité. L’implication de l’absorption intestinale d’endotoxines bactériennes du microbiote au cours de la digestion des lipides a été mise en évidence. Cependant la modulation de ces phénomènes par différentes quantités de lipides différemment structurés reste mal caractérisée, notamment chez les obèses. Nous avons mis en place un protocole clinique, en cross-over randomisé, visant à étudier chez des sujets normo-pondérés et obèses les conséquences de la digestion de matière grasse consommée, soit sous forme tartinée en différentes quantités (10 g ou 40 g), soit sous forme finement émulsionnée (40 g) sur le métabolisme postprandial des lipides et des endotoxines. Nous avons ainsi mis en évidence que l’augmentation plasmatique des chylomicrons, suite à une augmentation de la quantité de matière grasse ingérée, était plus précoce et plus importante chez les normo-pondérés que chez les sujets obèses, avec la sécrétion de plus gros chylomicrons suite à 40 g. Lorsque 40 g de matière grasse est émulsionnée, nous montrons qu’elle aboutit à un pic de triglycérides des chylomicrons plus précoce et plus élevé, reflétant une absorption facilitée des lipides, et de manière plus marquée chez l’obèse. Nous montrons aussi que cet état émulsionné aboutit à une β-oxydation plus élevée des lipides exogènes sur la journée, sans différence de perte fécale. Une endotoxémie postprandiale est également observée suite aux différents repas. L’accumulation postprandiale d’endotoxines, notamment présentes dans les chylomicrons, augmente avec la quantité de matière grasse tartinée en corrélation avec l’aire sous courbe des chylomicrons chez les obèses. En complément, l’absorption lipidique in vitro par des cellules Caco-2 était plus importante suite à l’incubation de milieux de lipolyse d’émulsions stabilisées par du caséinate que de la lécithine. Enfin, un test de digestion a été réalisé avant et après une chirurgie de by-pass gastrique pour identifier si une diminution drastique de l’absorption lipidique modifiait l’endotoxémie. Suite à l’opération, les patients sont davantage exposés aux endotoxines après la prise d’une émulsion au petit-déjeuner. En revanche, la LBP, protéine de transport des endotoxines proinflammatoire, diminue significativement à jeun et en postprandial suite à l’opération. L’ensemble de ces travaux démontrent qu’en plus des effets de la quantité de lipides ingérée sur la lipémie et l’absorption d’endotoxines associée, la structure de la matière grasse joue un rôle important dans la modulation du devenir métabolique des acides gras. La structuration des lipides alimentaires pourrait donc être spécifiquement adaptée afin d’optimiser le métabolisme lipidique postprandial, notamment chez des personnes obèses.The alteration of postprandial lipid metabolism and associated chronic inflammation emerge as major elements in the obesity pathophysiology. The involvement of the intestinal absorption of endotoxin from microbiota during lipid digestion was recently highlighted. However, the modulation of these phenomena by different amounts of differently structured lipids remains poorly characterized, especially in obese people. We developed a cross-over randomized clinical study to explore in normal weight and obese subjects the consequences of fat digestion, consumed either spread on bread in different amounts (10 g or 40 g) or finely emulsified (40 g), on postprandial metabolism of lipids and endotoxins. We have demonstrated that the increase in plasma chylomicrons, after increase in the amount of fat ingested, was earlier and greater in normal-weight than in obese subjects, with the secretion of larger chylomicrons after consumption of 40 g of spread fat. When 40 g of fat is emulsified, we show that it leads to an earlier and higher peak of chylomicron triglycerides, reflecting facilitated absorption of fat, and more significantly in obese subjects. We also show that emulsified fat results in higher β-oxidation of exogenous lipids over the day, with no difference in fecal excretion. Postprandial endotoxemia was also observed in response to different meals. The postprandial accumulation of endotoxins, present in chylomicrons, increases with the amount of spread fat ingested and it is correlated with the area under the curve of chylomicrons in obese subjects. In addition, the in vitro lipid absorption by Caco-2 cells was greater following incubation with lipolysis media of emulsions stabilized by caseinate than lecithin. Finally, a digestion test was conducted before and after gastric bypass surgery to identify whether a drastic reduction in lipid absorption altered metabolic endotoxemia. After surgery, patients are more exposed to endotoxins in the morning after emulsion consumption at breakfast. However, LBP, a proinflammatory protein transporting endotoxins, significantly decreases after surgery. Altogether, these studies demonstrate that in addition to the metabolic effects of dietary fat intake on lipemia and associated endotoxemia, the fat structure also plays an important role in the modulation of further fatty acid handling. Structuring of dietary lipids could thus be specifically adapted to optimize postprandial lipid metabolism, especially in obese people

Anhydrous Milk Fat enrichment with 13C-­triacylglycerol tracers: effects on thermal and structural behavior.

Dietary lipids are incorporated in food products under different types of structures, e.g., as dispersed lipid droplets (in oil -in -water emulsions, like creams) or as a continuous lipid phase (in water -in -oil emulsions, like butter for example). The crystallization, melting behavior and polymorphic stability of fats are determined by the behavior of the TAGs they contain. In clinical studies, there is a need to add some 13C TAGs as tracers to the ingested fats in order to track their metabolic fate. However, this procedure could modify the physicochemical properties of the fat. The present study was conducted in the framework of a clinical trial aiming at highlighting the effect of the physical structure of a fat (droplets in 0/W emulsion or bulk) in a meal on the absorption, chylomicron transport and further metabolic handling of dietary fatty acids (1). We therefore monitored the thermal and polymorphic behavior of anhydrous milk fat (AMF) enriched in tracers (a mixture of tripalmitin, triolein and tricaprylin; at 2 different concentrations: 1.5 and 5.7 wt%) using DSC and XRD and further compared it to the native AMF. The addition of 13C TAGs modified the AMF melting profile, especially at high concentration. The enriched AMF was completely melted at around 37°C, i.e. close to the body temperature. However, under some conditions, the AMF enriched in high 13C TAGs concentration remained crystallized at 37°C. Similar trends were observed in both systems (bulk vs emulsified). Moreover, AMF polymorphic behavior was also modified upon tracer addition. While only β’ form was observed in the native AMF, the 13 -form was detected in the AMF containing high 13C TAGs concentration. Importantly, low concentration of tracers should not have high impact on human digestive physiology. However more attention should be paid to physicochemical structure when high concentrations are added. (1) Vors et al. 2013. Modulating absorption and postprandial handling of dietary fatty acids by structuring fat in the meal: a randomized cross -over clinical trial. Am J Clin Nutr, 97(1): 23-36

Impact de la structure émulsionnée des lipides sur le devenir métabolique des acides gras alimentaires

In the human diet lipids are part of complex food products and are incorporated in various structures. Among the latter, emulsions are the most often employed in the food industry and clinical nutrition. Moreover, intestinal lipid absorption and post-absorptive phenomena during the postprandial phase play a major role in the onset and development of metabolic and cardiovascular diseases. However, the modulation of such phenomena by different structured dietary lipids remains poorly characterized, particularly among individuals with metabolic risk like obese subjects for whom the metabolic handling of dietary fatty acids is of utmost metabolic importance. The objective of this article is to review recent knowledge regarding the role and the metabolic impact of digestion and intestinal absorption of emulsified lipids and the nature of emulsifiers used as surface-active agents in emulsions. Our recent studies show that emulsified lipid structure can be a powerful tool to favor digestion, bioavailability and absorption of lipids and can modulate the imbalance of the metabolic handling of lipids in obese subjects, by favouring their beta-oxidation rather than their storage. Recent results on the potential metabolic consequences of different emulsifiers used for food emulsion formulation are also discussed. (C) 2016 Societe francaise de nutrition. Published by Elsevier Masson SAS. All rights reserved.Dans tout régime alimentaire, les lipides font partie constitutive d’aliments complexes et se retrouvent incorporés sous la forme de structures diverses. Parmi ces structures, ce sont les émulsions qui sont les plus représentées et employées en agroalimentaire et en nutrition clinique. Par ailleurs, l’absorption intestinale des lipides et les évènements post-absorptifs durant la période postprandiale jouent un rôle majeur dans l’initiation et le développement des maladies métaboliques et cardiovasculaires. Cependant la modulation de ces phénomènes par des lipides alimentaires différemment structurés reste peu caractérisée, notamment chez les sujets à risque comme les personnes obèses pour qui le fléchage métabolique des acides gras alimentaires est très important. L’objectif de cette revue est de faire le point sur les connaissances récentes concernant le rôle et l’impact métabolique de la digestion et l’absorption intestinale de lipides émulsionnés et la nature des émulsifiants qui composent ces émulsions. Nos travaux récents montrent que la structure émulsionnée est un levier potentiel pour favoriser la digestion, la biodisponibilité et l’absorption des lipides et moduler et corriger le déséquilibre du devenir métabolique des lipides chez l’obèse en favorisant leur utilisation plutôt que leur stockage. Des résultats récents sur les conséquences métaboliques potentielles de différents agents émulsifiants utilisés pour la formulation des émulsions alimentaires sont également discutés

Metabolic impact of dietary lipids: towards a role of unabsorbed lipid residues?

International audienceThe metabolic impact of dietary lipids needs to be considered beyond the fatty acid profile and energetic value of such lipids. Fatty acids are the building blocks of the different lipid molecules, including triacylglycerols and phospholipids, which are organized within various supramolecular structures such as emulsion droplets. These structures can also be naturally present or incorporated a posteriori in different food matrices. Gut health including its barrier function and microbiota is now recognized as a major player in cardiometabolic health. Even if more than 95% of dietary lipids are absorbed by the intestine to reach the bloodstream within the chylomicrons, a small proportion that is not absorbed is however able to interact with the microbiota and the cells of the distal intestine. The present non-exhaustive review will summarize briefly recent work on the impact of dietary lipids on absorption and their metabolic fate in the intestine, in particular on endotoxemia and low-grade inflammation related to obesity. Functional lipids are important ingredients used in food formulation and recent work has revealed the potential impact of some food emulsifiers on metabolism and inflammation in rodents in line with intestinal effects. Of particular interest in this review will be also recent findings on the benefits of dairy polar lipids on human lipid metabolism and their beneficial effects on metabolic inflammation in preclinical models. The review will also address the underlying mechanisms related to the metabolic fate of specific lipids such as sphingomyelin in the distal intestine, the microbiota and some actors of the intestinal barrier. Finally, these recent findings will be considered in the concept of the "food matrix effect" opening perspectives in the nutritional management of metabolic disorders

Impacts métaboliques et inflammatoires des matières grasses émulsionnées

International audienceThe health effects of lipids must now be explored beyond their energy content and fatty acid profile. Indeed, fatty acids as unit elements of different molecules such as triacylglycerols and phospholipids are being organized in various supramolecular structures such as emulsion droplets, and incorporated in complex food matrixes. This short article reviews our recent studies on the impact of fat emulsified structure on postprandial lipid metabolism and fatty acid beta-oxidation in normal-weight and obese humans, leading to the concept of "fast versus slow lipids". We also show how the postprandial kinetics of lipid absorption can contribute to modulate metabolic endotoxemia, partly arising from interactions between dietary lipids and gut microbiota, and able to contribute to metabolic inflammation in obesity. Finally, we highlight the pro-or anti-inflammatory impact in mice of surface active agents used in food formulation to stabilize emulsions, notably phospholipids of vegetal or dairy origin, and different molecular carriers of long-chain n-3 polyunsaturated fatty acids. The interested reader will refer to our other recent publications and reviews on these topics for a deeper insight into presented concepts

Dietary lipid emulsions and endotoxemia

The low-grade inflammation observed in obesity is a risk factor for cardiovascular diseases and insulin resistance. Among factors triggering such inflammation, recent works revealed the role of bacterial lipopolysaccharides (LPS), so-called endotoxins. LPS are naturally present in the gut via the intestinal microbiota. Recent studies show that they can induce in plasma a metabolic endotoxemia after the consumption of unbalanced hyperlipidic meals. This article reviews recent knowledge gained on the role of intestinal lipid absorption and the composition of dietary lipids on: (i) the induction of metabolic endotoxemia, (ii) the types of plasma transporters of LPS and (iii) associated low-grade inflammation. Notably, lipids are present in foods under various physicochemical structures and notably in emulsified form. Our recent works reveal that such structure and the type of emulsifier can modulate postprandial lipemia; recent results on the possible consequences on metabolic endotoxemia will be discussed

Dietary lipid emulsions and endotoxemia

The low-grade inflammation observed in obesity is a risk factor for cardiovascular diseases and insulin resistance. Among factors triggering such inflammation, recent works revealed the role of bacterial lipopolysaccharides (LPS), so-called endotoxins. LPS are naturally present in the gut via the intestinal microbiota. Recent studies show that they can induce in plasma a metabolic endotoxemia after the consumption of unbalanced hyperlipidic meals. This article reviews recent knowledge gained on the role of intestinal lipid absorption and the composition of dietary lipids on: (i) the induction of metabolic endotoxemia, (ii) the types of plasma transporters of LPS and (iii) associated low-grade inflammation. Notably, lipids are present in foods under various physicochemical structures and notably in emulsified form. Our recent works reveal that such structure and the type of emulsifier can modulate postprandial lipemia; recent results on the possible consequences on metabolic endotoxemia will be discussed