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Resume La composante inflammatoire des maladies metaboliques fait l’objet de nombreux travaux, avec les notions d’inflammation metabolique concernant le phenomene chronique de bas grade, ou encore d’inflammation postprandiale pour le phenomene transitoire observe suite a un repas. De nombreux biomarqueurs sont utilises et l’endotoxemie fait partie des facteurs d’interet. Le role des lipides alimentaires dans l’inflammation est tres discute. Les produits laitiers sont souvent decries pour leur teneur en acides gras satures susceptibles de favoriser l’inflammation. A ce jour, l’impact de ces produits sur l’inflammation postprandiale dependrait avant tout de la quantite consommee, et ce au meme titre que d’autres sources de lipides. De plus, aucun effet negatif de la consommation de produits laitiers sur l’inflammation chronique n’est a ce jour decrit ; trois etudes soulignent meme un effet protecteur chez des sujets minces a obeses. Dans une approche de nutrition preventive, l’etiologie de l’inflammation metabolique doit donc etre placee dans un contexte d’equilibre des regimes alimentaires.

Although short-term incubation of hepatocytes with oleic acid (OA) stimulates secretion of apolipoprotein B100 (apoB100), exposure to higher doses of OA for longer periods inhibits secretion in association with induction of endoplasmic reticulum (ER) stress. Palmitic acid (PA) induces ER stress, but its effects on apoB100 secretion are unclear. Docosahexaenoic acid (DHA) inhibits apoB100 secretion, but its effects on ER stress have not been studied. We compared the effects of each of these fatty acids on ER stress and apoB100 secretion in McArdle RH7777 (McA) cells: OA and PA induced ER stress and inhibited apoB100 secretion at higher doses; PA was more potent because it also increased the synthesis of ceramide. DHA did not induce ER stress but was the most potent inhibitor of apoB100 secretion, acting via stimulation of autophagy. These unique effects of each fatty acid were confirmed when they were infused into C57BL6J mice. Our results suggest that when both increased hepatic secretion of VLDL apoB100 and hepatic steatosis coexist, reducing ER stress might alleviate hepatic steatosis but at the expense of increased VLDL secretion. In contrast, increasing autophagy might reduce VLDL secretion without causing steatosis.

OBJECTIVE Obesity induces a program of systemic inflammation that is implicated in the development of many of its clinical sequelae. Hepatic inflammation is a feature of obesity-induced liver disease, and our previous studies demonstrated reduced hepatic steatosis in obese mice deficient in the C-C chemokine receptor 2 (CCR2) that regulates myeloid cell recruitment. This suggests that a myeloid cell population is recruited to the liver in obesity and contributes to nonalcoholic fatty liver disease. RESEARCH DESIGN AND METHODS We used fluorescence-activated cell sorting to measure hepatic leukocyte populations in genetic and diet forms of murine obesity. We characterized in vivo models that increase and decrease an obesity-regulated CCR2-expressing population of hepatic leukocytes. Finally, using an in vitro co-culture system, we measured the ability of these cells to modulate a hepatocyte program of lipid metabolism. RESULTS We demonstrate that obesity activates hepatocyte expression of C-C chemokine ligand 2 (CCL2/MCP-1) leading to hepatic recruitment of CCR2+ myeloid cells that promote hepatosteatosis. The quantity of these cells correlates with body mass and in obese mice represents the second largest immune cell population in the liver. Hepatic expression of CCL2 increases their recruitment and in the presence of dietary fat induces hepatosteatosis. These cells activate hepatic transcription of genes responsible for fatty acid esterification and steatosis. CONCLUSIONS Obesity induces hepatic recruitment of a myeloid cell population that promotes hepatocyte lipid storage. These findings demonstrate that recruitment of myeloid cells to metabolic tissues is a common feature of obesity, not limited to adipose tissue.

ER stress can cause hepatic insulin resistance and steatosis. Increased VLDL secretion could protect the liver from ER stress-induced steatosis, but the effect of lipid-induced ER stress on the secretion of VLDL is unknown. To determine the effect of lipids on hepatic ER stress and VLDL secretion, we treated McA-RH7777 liver cells with free fatty acids. Prolonged exposure increased cell triglycerides, induced steatosis, and increased ER stress. Effects on apoB100 secretion, which is required for VLDL assembly, were parabolic, with moderate free fatty acid exposure increasing apoB100 secretion, while greater lipid loading inhibited apoB100 secretion. This decreased secretion at higher lipid levels was due to increased protein degradation through both proteasomal and nonproteasomal pathways and was dependent on the induction of ER stress. These findings were supported in vivo, where intravenous infusion of oleic acid (OA) in mice increased ER stress in a duration-dependent manner. apoB secretion was again parabolic, stimulated by moderate, but not prolonged, OA infusion. Inhibition of ER stress was able to restore OA-stimulated apoB secretion after prolonged OA infusion. These results suggest that excessive ER stress in response to increased hepatic lipids may decrease the ability of the liver to secrete triglycerides by limiting apoB secretion, potentially worsening steatosis.

Visceral adipose tissue and skeletal muscle have central roles in determining whole-body insulin sensitivity. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a potential mediator of insulin sensitivity. It can directly modulate the expression of genes that are involved in glucose and lipid metabolism, including GLUT4, lipoprotein lipase (LPL) and adipocytokines (leptin and adiponectin). In this study, we aimed to determine the effects of obesity-associated insulin resistance on mRNA expression of PPARgamma and its target genes. Dogs were studied when they were lean and at the end of an overfeeding period when they had reached a steady obese state. The use of a sensitive, real-time PCR assay allowed a relative quantification of mRNA expression for PPARgamma, LPL, GLUT4, leptin and adiponectin, in adipose tissue and skeletal muscle. In visceral adipose tissue and/or skeletal muscle, mRNA expression of PPARgamma, LPL and GLUT4 were at least 2-fold less in obese and insulin-resistant dogs compared with the same animals when they were lean and insulin-sensitive. The mRNA expression and plasma concentration of leptin was increased, whereas the plasma level and mRNA expression of adiponectin was decreased, by obesity. In adipose tissue, PPARgamma expression was correlated with leptin and adiponectin. These findings, in an original model of obesity induced by a prolonged period of overfeeding, showed that insulin resistance is associated with a decrease in PPARgamma mRNA expression that could dysregulate expression of several genes involved in glucose and lipid metabolism.

The effects of ruminant (R)trans-fatty acids (TFA) on the risk of CVD are still under debate. It could be argued that the lack of the effect of R-TFA may be the result of the small amount of their intake. Taking into consideration the growing available data from intervention studies, we carried out a systematic review and meta-regression to assess the impact of R-TFA intake levels on changes in the total cholesterol: HDL-cholesterol (TC:HDL-C) ratio. A systematic review of the literature was conducted and thirteen randomised clinical trials were included, yielding a total of twenty-three independent experimental groups of subjects. A univariate random-effects meta-regression approach was used to quantify the relationship between the dose of R-TFA and changes in the TC:HDL-C ratio. To consider several potential modifiers such as subject and dietary characteristics, a multivariate regression analysis was performed. We found no relationship between R-TFA intake levels of up to 4·19 % of daily energy intake (EI) and changes in cardiovascular risk factors such as TC:HDL-C and LDL-cholesterol (LDL-C):HDL-C ratios. In addition, a multivariate regression analysis that included other dietary variables, as well as subject baseline characteristics, confirmed that doses of R-TFA did not significantly influence the changes in the lipid ratio. Our findings showed that doses of R-TFA did not influence the changes in the ratios of plasma TC:HDL-C and LDL-C:HDL-C. These data suggest that TFA from natural sources, at least at the current levels of intake and up to 4·19 % EI, have no adverse effects on these key CVD risk markers in healthy people.

This review is respectfully dedicated to the memory of Michel Ollivon, Research Director at CNRS (Châtenay-Malabry, France), outstanding physico-chemist specialist of lipid organization, recipient of the Hilditch Memorial Lecture award, who was the initiator of the network RMT LISTRAL. We are also sadly paying tribute to Jean-Luc Vendeuvre, Food Engineer at the French Pork and Pig Institute (IFIP, Maisons-Alfort, France), outstanding expert in meat products who participated actively in RMT LISTRAL and provided unpublished data for figures in the present review, who passed away during review submission. RMT LISTRAL: Mixed Technological Network combining academic and industrial partners, devoted to the enhancement and divulgation of knowledge regarding structured dietary lipids.; International audience; On a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen.

Revue réalisée en hommage à Michel Ollivon (Directeur de Recherche au CNRS, UMR8612, Châtenay-Malabry), décédé en juin 2007, qui a été à l’origine de la création du RMT Listral. Ce Réseau Mixte Technologique avec pour thématique les Lipides Structurés Alimentaires est coordonné par l’ACTIA et animé par Actilait. Les autres partenaires du réseau sont : F Sobolewski & JP Bodin (Enilia-Ensmic), K Duhem & JP Guyonnet (Cniel), JP Bergé & JP Gouygou (Ifremer Nantes), G Nassy (Ifip), Lebois & D Majou (Actia), P Gaborit & R Richoux (Actilait).; National audience; From the nutrition point of view, lipids are primarily considered as energy suppliers, their dietary intake having to be limited. In fact, lipids are sources of various fatty acids, and dietary recommendations include the required daily intakes in different fatty acids (fatty acid profile). Beyond these quantitative aspects, fatty acids are part of larger molecules, mainly triacylglycerols (TAG), that are organized in supramolecular structures as for example fat crystals and lipid droplets. Recent advances in nutrition research have demonstrated that these structures, and lipid organization in food matrices, influence digestibility and metabolism of fatty acids. Therefore, the members of the technological network Listral propose a synthesis of the knowledge about the influence of molecular and supramolecular structures of lipids on digestion and metabolic fate of dietary fatty acids originating from for the main food industry sectors. Fatty acids are mainly provided in the diet in the form of TAG, or phospholipids (PL) where they are esterified in external (sn-1, sn-3) or internal (sn-2) position of the glycerol backbone. They can also be found as ethyl esters (EE) in specific formulations. These molecular characteristics of the lipid molecules affect their hydrolysis and their absorption rate but also their metabolism in indifferent organs, as assessed in studies often using inter esterified fat sources. The results depend on the types of fatty acids (saturated or polyunsaturated fatty acids) but also on the model used for the studies: in vitro or in vivo studies ; animal model, human newborn or adult, either healthy or exhibiting some diseases. Among others, it was found that the crystal form and fat melting point as affected by the fatty acid profiles and the lipid molecular structures directly impact fatty acid absorption kinetics through modifications of lipolytic enzyme activities. However, in these studies, the relative effect of the thermal properties of lipids and the proportion of saturated fatty acids chains in sn-2 position were hardly distinguished. Supramolecular structures, namely type and size of the fat droplets and their interfacial composition, of lipids, either in their native forms or obtained after food processes, also affect the digestibility and absorption of lipids. This aspect is reviewed with specific focus on dairy, marine, meat, oil plant and egg products. The impact of other nutritional components present in these food matrices on the absorption of lipids is also discussed.