Link between Intestinal CD36 Ligand Binding and Satiety Induced by a High Protein Diet in Mice

CD36 is a ubiquitous membrane glycoprotein that binds long-chain fatty acids. The presence of a functional CD36 is required for the induction of satiety by a lipid load and its role as a lipid receptor driving cellular signal has recently been demonstrated. Our project aimed to further explore the role of intestinal CD36 in the regulation of food intake. Duodenal infusions of vehicle or sulfo-N-succinimidyl-oleate (SSO) was performed prior to acute infusions of saline or Intralipid (IL) in mice. Infusion of minute quantities of IL induced a decrease in food intake (FI) compared to saline. Infusion of SSO had the same effect but no additive inhibitory effect was observed in presence of IL. No IL- or SSO-mediated satiety occurred in CD36-null mice. To determine whether the CD36-mediated hypophagic effect of lipids was maintained in animals fed a satietogen diet, mice were subjected to a High-Protein diet (HPD). Concomitantly with the satiety effect, a rise in intestinal CD36 gene expression was observed. No satiety effect occurred in CD36-null mice. HPD-fed WT mice showed a diminished FI compared to control mice, after saline duodenal infusion. But there was no further decrease after lipid infusion. The lipid-induced decrease in FI observed on control mice was accompanied by a rise in jejunal oleylethanolamide (OEA). Its level was higher in HPD-fed mice than in controls after saline infusion and was not changed by lipids. Overall, we demonstrate that lipid binding to intestinal CD36 is sufficient to produce a satiety effect. Moreover, it could participate in the satiety effect induced by HPD. Intestine can modulate FI by several mechanisms including an increase in OEA production and CD36 gene expression. Furthermore, intestine of mice adapted to HPD have a diminished capacity to modulate their food intake in response to dietary lipids

Extraction of pure components from overlapped signals in gas chromatography-mass spectrometry (GC-MS)

Gas chromatography-mass spectrometry (GC-MS) is a widely used analytical technique for the identification and quantification of trace chemicals in complex mixtures. When complex samples are analyzed by GC-MS it is common to observe co-elution of two or more components, resulting in an overlap of signal peaks observed in the total ion chromatogram. In such situations manual signal analysis is often the most reliable means for the extraction of pure component signals; however, a systematic manual analysis over a number of samples is both tedious and prone to error. In the past 30 years a number of computational approaches were proposed to assist in the process of the extraction of pure signals from co-eluting GC-MS components. This includes empirical methods, comparison with library spectra, eigenvalue analysis, regression and others. However, to date no approach has been recognized as best, nor accepted as standard. This situation hampers general GC-MS capabilities, and in particular has implications for the development of robust, high-throughput GC-MS analytical protocols required in metabolic profiling and biomarker discovery. Here we first discuss the nature of GC-MS data, and then review some of the approaches proposed for the extraction of pure signals from co-eluting components. We summarize and classify different approaches to this problem, and examine why so many approaches proposed in the past have failed to live up to their full promise. Finally, we give some thoughts on the future developments in this field, and suggest that the progress in general computing capabilities attained in the past two decades has opened new horizons for tackling this important problem

Single-molecule kinetics of pore assembly by the membrane attack complex

The membrane attack complex (MAC) is a hetero-oligomeric protein assembly that kills pathogens by perforating their cell envelopes. The MAC is formed by sequential assembly of soluble complement proteins C5b, C6, C7, C8 and C9, but little is known about the rate-limiting steps in this process. Here, we use rapid atomic force microscopy (AFM) imaging to show that MAC proteins oligomerize within the membrane, unlike structurally homologous bacterial pore-forming toxins. C5b-7 interacts with the lipid bilayer prior to recruiting C8. We discover that incorporation of the first C9 is the kinetic bottleneck of MAC formation, after which rapid C9 oligomerization completes the pore. This defines the kinetic basis for MAC assembly and provides insight into how human cells are protected from bystander damage by the cell surface receptor CD59, which is offered a maximum temporal window to halt the assembly at the point of C9 insertion

Dynamics and fates of trace metals chronically input in a Mediterranean coastal zone impacted by a large urban area

International audienceQuantification and characterization of chronic inputs of trace metals and organic carbon in a coastal Med-iterranean area (the city of Marseille) during the dry season was carried out. The 625 km 2 watershed includes two small coastal rivers whose waters are mixed with treated wastewater (TWW) just before their outlet into the sea. Dissolved and particulate Cu, Pb, Cd, Zn, Co, Ni and organic carbon concentra-tions in the rivers were comparable to those in other Mediterranean coastal areas, whereas at the outlet, 2-to 18-fold higher concentrations reflected the impact of the TWW. A non-conservative behavior observed for most of the studied metals in the mixing zone was validated by a remobilization experiment performed in the laboratory. The results showed that sorption/desorption processes could occur with slow kinetics with respect to the mixing time in the plume, indicating non-equilibrium in the dis-solved/particulate metal distribution. Thus, a sample filtration immediately after sampling is strictly required

Flood inputs in a Mediterranean coastal zone impacted by a large urban area: Dynamic and fate of trace metals

Trace elements and organic carbon inputs to the Mediterranean sea from an urbanized area (Marseille city) were studied and characterized during flood events. Inputs were brought to the sea by two small coastal rivers whose waters were mixed together and also with treated wastewaters (TWW) just before discharge. The monitoring of the rivers during flood events showed the high temporal dynamics of water flow, suspended particulate matter (SPM), organic carbon and trace metals concentrations, typical of small coastal Mediterranean rivers and requiring an appropriate sampling strategy. Dissolved/particulate partition coefficient (log Kd) in rivers during floods remained quasi-constant for a given trace element, but differed from one element to another according to their affinity toward particles. Because of high SPM concentrations, trace elements were mainly brought to the sea during floods as particles, despite a weaker affinity for particles when compared to baseflow conditions for all studied elements but Pb. If the contribution of TWW dominated the elements baseflow discharge to the coastal zone, rivers outweighed during floods. When discharged to the sea, most trace elements underwent partial desorption in the salinity gradient, especially at highest salinity. Laboratory desorption experiments results were consistent with field data and showed slower desorption kinetics than in baseflow conditions, suggesting that trace elements desorption rates from particles are slower than sedimentation rates. With regard to heavy particles, it results in a potential impact of the sediment on benthic organisms and a possible further desorption after sediment resuspension events. With regard to light particles, it results possible additional desorption during offshore transport

Over-expression of the epidermis-specific HD-ZIP IV transcription factor OCL1 in maize identifies target genes involved in lipid metabolism and cuticle biosynthesis.

International audienc

Behaviour and fate of urban particles in coastal waters: Settling rate, size distribution and metals contamination characterization

The evaluation of contaminant net fluxes from the coast to the open sea requires the study of terrigeneous particles behaviour and fate. We studied the particles issued from two small coastal rivers whose waters are mixed with treated wastewater (TWW) coming from the Marseille wastewater treatment plant (WWTP) just before discharge to the Mediterranean Sea. An experimental device was developed and used to investigate particles settling rates, size distribution and metallic contamination when mixing with seawater. The particles were sampled in flood deposits of rivers and outlets during rainy periods and in the outlet water during dry periods. The flood deposits were mainly composed of 50–200 μm-sized particles, higher metals content being observed in the finest fractions. Dry period particles showed the stronger influence of wastewater inputs. Al, Ca, Cs, Li, Rb, Ti, and Tl were mainly of terrigeneous origin, whereas Ag, Ba, Cd, Cr, Cu, Hg, Mg, Mo, Ni, Pb, POC, Sb, Sn and Zn were of anthropogenic origin, issued from non-treated sewage, TWW or industrial waste. In seafloor sediments, all metals exhibited a continuous increase of concentration from the outlet to, at least, 800 m offshore. Implementation of settling particles characteristics in a 3D hydrodynamic and sediment transport model reproduced well the observed deposition of polluted particles in the coastal zone and indicated a non-negligible offshore export of the finest particles and their accompanying pollutants