Serum Metabolites Responding in a Dose-Dependent Manner to the Intake of a High-Fat Meal in Normal Weight Healthy Men Are Associated with Obesity.

Although the composition of the human blood metabolome is influenced both by the health status of the organism and its dietary behavior, the interaction between these two factors has been poorly characterized. This study makes use of a previously published randomized controlled crossover acute intervention to investigate whether the blood metabolome of 15 healthy normal weight (NW) and 17 obese (OB) men having ingested three doses (500, 1000, 1500 kcal) of a high-fat (HF) meal can be used to identify metabolites differentiating these two groups. Among the 1024 features showing a postprandial response, measured between 0 h and 6 h, in the NW group, 135 were dose-dependent. Among these 135 features, 52 had fasting values that were significantly different between NW and OB men, and, strikingly, they were all significantly higher in OB men. A subset of the 52 features was identified as amino acids (e.g., branched-chain amino acids) and amino acid derivatives. As the fasting concentration of most of these metabolites has already been associated with metabolic dysfunction, we propose that challenging normal weight healthy subjects with increasing caloric doses of test meals might allow for the identification of new fasting markers associated with obesity.

Identification of Milk and Cheese Intake Biomarkers in Healthy Adults Reveals High Interindividual Variability of Lewis System-Related Oligosaccharides.

BACKGROUND: The use of biomarkers of food intake (BFIs) in blood and urine has shown great promise for assessing dietary intake and complementing traditional dietary assessment tools whose use is prone to misreporting. OBJECTIVE: Untargeted LC-MS metabolomics was applied to identify candidate BFIs for assessing the intake of milk and cheese and to explore the metabolic response to the ingestion of these foods. METHODS: A randomized controlled crossover study was conducted in healthy adults [5 women, 6 men; age: 23.6 ± 5.0 y; BMI (kg/m2): 22.1 ± 1.7].  After a single isocaloric intake of milk (600 mL), cheese (100 g), or soy-based drink (600 mL), serum and urine samples were collected postprandially up to 6 h and after fasting after 24 h. Untargeted metabolomics was conducted using LC-MS. Discriminant metabolites were selected in serum by multivariate statistical analysis, and their mass distribution and postprandial kinetics were compared. RESULTS: Serum metabolites discriminant for cheese intake had a significantly lower mass distribution than metabolites characterizing milk intake (P = 4.1 × 10-4). Candidate BFIs for milk or cheese included saccharides, a hydroxy acid, amino acids, amino acid derivatives, and dipeptides. Two serum oligosaccharides, blood group H disaccharide (BGH) and Lewis A trisaccharide (LeA), specifically reflected milk intake but with high interindividual variability. The 2 oligosaccharides showed related but opposing trends: subjects showing an increase in either oligosaccharide did not show any increase in the other oligosaccharide. This result was confirmed in urine. CONCLUSIONS: New candidate BFIs for milk or cheese could be identified in healthy adults, most of which were related to protein metabolism. The increase in serum of LeA and BGH after cow-milk intake in adults calls for further investigations considering the beneficial health effects on newborns of such oligosaccharides in maternal milk. The trial is registered at clinicaltrials.gov as NCT02705560.

Artificial Lysosomal Platform to Study Nanoparticle Long-term Stability.

Nanoparticles (NPs) possess unique properties useful for designing specific functionalities for biomedi- cal applications. A prerequisite of a safe-by-design and effective use in any biomedical application is to study NP-cell interactions to gain a better understanding of cellular consequences upon exposure. Cellular uptake of NPs results mainly in the localization of NPs in the complex environment of lysosomes, a compartment which can be mimicked by artificial lysosomal fluid. In this work we showed the applicability of lysosomal fluid as a platform for a fast assessment of gold, iron oxide and silica NP stability over 24 h in a relevant biological fluid, by using multiple analytical methods.

Beyond Global Charge: Role of Amine Bulkiness and Protein Fingerprint on Nanoparticle-Cell Interaction.

Amino groups presented on the surface of nanoparticles are well-known to be a predominant factor in the formation of the protein corona and subsequent cellular uptake. However, the molecular mechanism underpinning this relationship is poorly defined. This study investigates how amine type and density affect the protein corona and cellular association of gold nanoparticles with cells in vitro. Four specific poly(vinyl alcohol-co-N-vinylamine) copolymers are synthesized containing primary, secondary, or tertiary amines. Particle cellular association (i.e., cellular uptake and surface adsorption), as well as protein corona composition, are then investigated. It is found that the protein corona (as a consequence of "amine bulkiness") and amine density are both important in dictating cellular association. By evaluating the nanoparticle surface chemistry and the protein fingerprint, proteins that are significant in mediating particle-cell association are identified. In particular, primary amines, when exposed on the polymer side chain, are strongly correlated with the presence of alpha-2-HS-glycoprotein, and promote nanoparticle cellular association.

Polyvinyl alcohol as a biocompatible alternative for the passivation of gold nanorods.

The functionalization of gold nanorods (GNRs) with polymers is essential for both their colloidal stability and biocompatibility. However, a bilayer of the toxic cationic surfactant cetyl trimethylammonium bromide (CTAB) adsorbed on the nanorods complicates this process. Herein, we report on a strategy for the biocompatible functionalization of GNRs with a hydrophobic polymeric precursor, polyvinyl acetate, which is then transformed into its hydrophilic analogue, polyvinyl alcohol. This polymer was chosen due to its well-established biocompatibility, tunable "stealth" properties, tunable hydrophobicity, and high degree of functionality. The biocompatibility of the functionalized GNRs was tested by exposing them to primary human blood monocyte derived macrophages; the advantages of tunable hydrophobicity were demonstrated with the long-term stable encapsulation of a model hydrophobic drug molecule.