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

Identification of new binding partners of the chemosensory signaling protein Gγ13 expressed in taste and olfactory sensory cells

Tastant detection in the oral cavity involves selective receptors localized at the apical extremity of a subset of specialized taste bud cells called taste receptor cells (TRCs). The identification of the genes coding for the taste receptors involved in this process have greatly improved our understanding of the molecular mechanisms underlying detection. However, how these receptors signal in TRCs, and whether the components of the signaling cascades interact with each other or are organized in complexes is mostly unexplored. Here we report on the identification of three new binding partners for the mouse G protein gamma 13 subunit (Gγ13), a component of the bitter taste receptors signaling cascade. For two of these Gγ13 associated proteins, namely GOPC and MPDZ, we describe the expression in taste bud cells for the first time. Furthermore, we demonstrate by means of a yeast two-hybrid interaction assay that the C terminal PDZ binding motif of Gγ13 interacts with selected PDZ domains in these proteins. In the case of the PDZ domain-containing protein zona occludens-1 (ZO-1), a major component of the tight junction defining the boundary between the apical and baso-lateral region of TRCs, we identified the first PDZ domain as the site of strong interaction with Gγ13. This association was further confirmed by co-immunoprecipitation experiments in HEK 293 cells. In addition, we present immunohistological data supporting partial co-localization of GOPC, MPDZ, or ZO-1, and Gγ13 in taste buds cells. Finally, we extend this observation to olfactory sensory neurons (OSNs), another type of chemosensory cells known to express both ZO-1 and Gγ13. Taken together our results implicate these new interaction partners in the sub-cellular distribution of Gγ13 in olfactory and gustatory primary sensory cells

Ric-8A, a Gα Protein Guanine Nucleotide Exchange Factor Potentiates Taste Receptor Signaling

Taste receptors for sweet, bitter and umami tastants are G-protein-coupled receptors (GPCRs). While much effort has been devoted to understanding G-protein-receptor interactions and identifying the components of the signalling cascade downstream of these receptors, at the level of the G-protein the modulation of receptor signal transduction remains relatively unexplored. In this regard a taste-specific regulator of G-protein signaling (RGS), RGS21, has recently been identified. To study whether guanine nucleotide exchange factors (GEFs) are involved in the transduction of the signal downstream of the taste GPCRs we investigated the expression of Ric-8A and Ric-8B in mouse taste cells and their interaction with G-protein subunits found in taste buds. Mammalian Ric-8 proteins were initially identified as potent GEFs for a range of Gα subunits and Ric-8B has recently been shown to amplify olfactory signal transduction. We find that both Ric-8A and Ric-8B are expressed in a large portion of taste bud cells and that most of these cells contain IP3R-3 a marker for sweet, umami and bitter taste receptor cells. Ric-8A interacts with Gα-gustducin and Gαi2 through which it amplifies the signal transduction of hTas2R16, a receptor for bitter compounds. Overall, these findings are consistent with a role for Ric-8 in mammalian taste signal transduction

Metabolic endotoxemia: a potential underlying mechanism of the relationship between dietary fat intake and risk for cognitive impairments in humans?

(1) Background: Nutrition is a major lifestyle factor that can prevent the risk of cognitive impairment and dementia. Diet-induced metabolic endotoxemia has been proposed as a major root cause of inflammation and these pathways emerge as detrimental factors of healthy ageing. The aim of this paper was to update research focusing on the relationship between a fat-rich diet and endotoxemia, and to discuss the potential role of endotoxemia in cognitive performances. [br/] (2) Methods: We conducted a non-systematic literature review based on the PubMed database related to fat-rich meals, metabolic endotoxemia and cognitive disorders including dementia in humans. A total of 40 articles out of 942 in the first screening met the inclusion criteria. [br/] (3)Results: Evidence suggested that a fat-rich diet, depending on its quality, quantity and concomitant healthy food components, could influence metabolic endotoxemia. Since only heterogeneous cross-sectional studies are available, it remains unclear to what extent endotoxemia could be associated or not with cognitive disorders and dementia. [br/] (4)Conclusions: A fat-rich diet has the capability to provide significant increases in circulating endotoxins, which highlights nutritional strategies as a promising area for future research on inflammatory-associated diseases. The role of endotoxemia in cognitive disorders and dementia remains unclear and deserves further investigation

Impact de la quantité et de la structure des matières grasses ingérées sur l'endotoxémie métabolique issue du microbiote chez l'homme obèse vs normopondéré

Impact de la quantité et de la structure des matières grasses ingérées sur l'endotoxémie métabolique issue du microbiote chez l'homme obèse vs normopondéré. Journées Francophones de Nutrition (JFN 2017

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

Metabolic and inflammatory impacts of emulsified fats and oils

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, 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 vs 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. (C) 2017 Published by Elsevier Masson SAS on behalf of Societe francaise de nutrition