Mireille Moser

Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism

Recent studies showed that germ-free (GF) mice are resistant to obesity when consuming a high-fat, high-carbohydrate Western diet. However, it remains unclear what mechanisms are involved in the antiobesity phenotype and whether GF mice develop insulin resistance and dyslipidemia with high-fat (HF) feeding. In the present study, we compared the metabolic consequences of HF feeding on GF and conventional (conv) C57BL/6J mice. GF mice consumed fewer calories, excreted more fecal lipids, and weighed significantly less than conv mice. GF/HF animals also showed enhanced insulin sensitivity with improved glucose tolerance, reduced fasting and nonfasting insulinemia, and increased phospho-Akt((Ser-473)) in adipose tissue. In association with enhanced insulin sensitivity, GF/HF mice had reduced plasma TNF-α and total serum amyloid A concentrations. Reduced hypercholesterolemia, a moderate accretion of hepatic cholesterol, and an increase in fecal cholesterol excretion suggest an altered cholesterol metabolism in GF/HF mice. Pronounced nucleus SREBP2 proteins and up-regulation of cholesterol biosynthesis genes indicate that enhanced cholesterol biosynthesis contributed to the cholesterol homeostasis in GF/HF mice. Our results demonstrate that fewer calorie consumption and increased lipid excretion contributed to the obesity-resistant phenotype of GF/HF mice and reveal that insulin sensitivity and cholesterol metabolism are metabolic targets influenced by the gut microbiota.

Lactococcus lactis NCC 2287 Alleviates Food Allergic Manifestations in Sensitized Mice by Reducing IL-13 Expression Specifically in the Ileum

Objective. Utilizing a food allergy murine model, we have investigated the intrinsic antiallergic potential of the Lactococcus lactis NCC 2287 strain. Methods. BALB/c mice were sensitized at weekly intervals with ovalbumin (OVA) plus cholera toxin (CT) by the oral route for 7 weeks. In this model, an oral challenge with a high dose of OVA at the end of the sensitization period leads to clinical symptoms. Lactococcus lactis NCC 2287 was given to mice via the drinking water during sensitization (prevention phase) or after sensitization (management phase). Results. Lactococcus lactis NCC 2287 administration to sensitized mice strikingly reduced allergic manifestations in the management phase upon challenge, when compared to control mice. No preventive effect was observed with the strain. Lactococcus lactis NCC 2287 significantly decreased relative expression levels of the Th-2 cytokine, IL-13, and associated chemokines CCL11 (eotaxin-1) and CCL17 (TARC) in the ileum. No effect was observed in the jejunum. Conclusion/Significance. These results taken together designate Lactococcus lactis NCC 2287 as a candidate probiotic strain appropriate in the management of allergic symptoms.

Validation of a new hand-held electronic appetite rating system against the pen and paper method.

This study describes the validation of a new electronic appetite rating system, and a statistical variance model for visual analogue scale (VAS) research. Thirty volunteers rated hunger, fullness, desire to eat, prospective intake, thirst and liking on 100mm paper VAS and on 70 mm electronic VAS presented on a Dell Pocket PC, after consuming breakfast, in a repeated trial. The electronic method was comparable in relative accuracy and reproducibility to the paper method, with weak differences between tests (within-subject SD < or =14 mm). The data obtained were used to generate a model for VAS data variability.

Consequences of Exchanging Carbohydrates for Proteins in the Cholesterol Metabolism of Mice Fed a High-fat Diet

Consumption of low-carbohydrate, high-protein, high-fat diets lead to rapid weight loss but the cardioprotective effects of these diets have been questioned. We examined the impact of high-protein and high-fat diets on cholesterol metabolism by comparing the plasma cholesterol and the expression of cholesterol biosynthesis genes in the liver of mice fed a high-fat (HF) diet that has a high (H) or a low (L) protein-to-carbohydrate (P/C) ratio. H-P/C-HF feeding, compared with L-P/C-HF feeding, decreased plasma total cholesterol and increased HDL cholesterol concentrations at 4-wk. Interestingly, the expression of genes involved in hepatic steroid biosynthesis responded to an increased dietary P/C ratio by first down-regulation (2-d) followed by later up-regulation at 4-wk, and the temporal gene expression patterns were connected to the putative activity of SREBF1 and 2. In contrast, Cyp7a1, the gene responsible for the conversion of cholesterol to bile acids, was consistently up-regulated in the H-P/C-HF liver regardless of feeding duration. Over expression of Cyp7a1 after 2-d and 4-wk H-P/C-HF feeding was connected to two unique sets of transcription regulators. At both time points, up-regulation of the Cyp7a1 gene could be explained by enhanced activations and reduced suppressions of multiple transcription regulators. In conclusion, we demonstrated that the hypocholesterolemic effect of H-P/C-HF feeding coincided with orchestrated changes of gene expressions in lipid metabolic pathways in the liver of mice. Based on these results, we hypothesize that the cholesterol lowering effect of high-protein feeding is associated with enhanced bile acid production but clinical validation is warranted. (246 words)

Natural carbon isotope abundance of plasma metabolites and liver tissue differs between diabetic and non-diabetic Zucker diabetic fatty rats.

Background ‘You are what you eat’ is an accurate summary for humans and animals when it comes to carbon isotope abundance. In biological material, natural13C/12C ratio is subject to minute variations due to diet composition (mainly from ingestion of C3 and C4 metabolism plants) and to the discrimination between ‘light’ and ‘heavy’ isotopes during biochemical reactions (isotope effects and isotopic fractionation). Methodology/Principal Findings Carbon isotopic abundance was measured in ZDF (fa/+) and ZDF (fa/fa), (lean and obese-diabetic rats respectively) fed the same diet. By analysing plasma metabolites (glucose and non-esterified fatty acids), breath and liver tissue by high-precision isotope ratio mass spectrometry, we demonstrate for the first time statistically distinguishable metabolic carbon isotope abundance between ZDF (fa/+) and ZDF (fa/fa) rats based on plasma glucose, palmitic, oleic, linoleic, arachidonic acids and bulk analysis of liver tissue (P<0.005) resulting into clear isotopic fingerprints using principal component analysis. We studied the variation of isotopic abundance between both groups for each metabolite and through the metabolic pathways using the precursor/product approach. We confirmed that lipids were depleted in 13C compared to glucose in both genotypes. We found that isotopic abundance of linoleic acid (C18: 2n-6), even though both groups had the same feed, differed significantly between both groups. The likely reason for these changes between ZDF (fa/+) and ZDF (fa/fa) are metabolic dysregulation associated with various routing and fluxes of metabolites. Conclusion/Significance This work provides evidence that measurement of natural abundance isotope ratio of both bulk tissue and individual metabolites can provide meaningful information about metabolic changes either associated to phenotype or to genetic effects; irrespective of concentration. In the future measuring the natural abundance δ13C of key metabolites could be used as endpoints for studying in vivo metabolism, especially with regards to metabolic dysregulation, and development and progression of metabolic diseases.

Differing structural properties of foods affect the development of mandibular control and muscle coordination in infants and young children

The development of chewing is an essential motor skill that is continually refined throughout early childhood. From a motor control perspective, the advancement of textures is dependent upon the fit between a childs oral anatomic and motor system and food properties. The purpose of this exploratory study is to identify age-related changes in chewing motor coordination and control and to determine if these changes are associated with the differing structural properties of solid foods, as well as to explore the role of explanatory variables such as the emergence of teeth and bite force. The masticatory muscle coordination (i.e., coupling of synergistic and antagonistic muscle pairs) and control (i.e., speed, displacement, chewing rate, duration, and number of chews) of fifty children were assessed cross-sectionally at five ages: 9-, 12-, 18-, 24-, and 36-months using electromyography (EMG) and 3D optical motion capture while children ate three foods that had differing structural properties. The results of this study found that children made gains in their chewing motor control (decreased duration of chewing sequences and lateral jaw displacement) and coordination (improved jaw muscle coupling) throughout this period. The structural differences in foods also affected chewing performance at all ages. These preliminary findings suggest that some solid textures are better adapted for immature mandibular control than others and that the development of chewing is a protracted process that may be impacted by the emergence of teeth and changes to bite force.

Advanced Analytical Sensory Correlation – Towards a Better Molecular Understanding of Coffee Flavor

The present study aimed at better understanding the link between the sensory profile of espresso coffees and their molecular aroma and taste composition. Twelve coffee blends were assessed by instrumental analysis and sensory profiling. The results were statistically correlated using a knowledge-based standardization and normalization of both datasets that selectively extracts differences in the quality of samples, while reducing the impact of variations on the overall intensity of coffees. Several of the 42 aroma and 12 taste compounds analyzed for this study exhibited a good correlation with specific sensory descriptors and may be used as chemical markers. In addition, a robust mathematical model could be developed that predicts the sensory profile of espresso coffees from instrumental data. Such model is a very useful tool for future development of coffee blends with tailored flavor profiles. The results represent significant progress in correlating sensory with instrumental data, exemplified on one of the most complex aromas, i.e., coffee.

UV-C inactivation of foodborne bacterial and viral pathogens and surrogates on fresh and frozen berries

Outbreaks of foodborne illness associated with berries often involve contamination with hepatitis A virus (HAV) and norovirus but also bacteria such as Escherichia coli O157:H7 and parasites such as Cyclospora caytanensis. We evaluated the applicability of UV-C to the inactivation of pathogens on strawberries, raspberries and blueberries. Our three-step approach consisted of assessing the chemical safety of UV-C-irradiated berries, evaluating the sensory quality after UV-C treatment and finally studying the inactivation of the target microorganisms. Treatments lasting up to 9 min (4000 mJ cm-2) did not produce detectable levels of furan (<5 μg/kg), a known photolysis product of fructose with genotoxic activity and thus were assessed to be toxicologically safe. No effect on taste or appearance was observed, unless treatment was excessively long. 20 s of treatment (an average fluence of ~ 212 mJ cm-2) reduced active HAV titer by >1 log10 unit in 95% of cases except on frozen raspberries, while 120 s were required to inactivate murine norovirus to this extent on fresh blueberries. The mean inactivation of HAV and MNV was greater on blueberries (2-3 log10) than on strawberries and raspberries (<2 log10). MNV was more sensitive on fresh than on frozen berries, unlike HAV. Inactivation of Salmonella, E. coli O157:H7 and Listeria monocytogenes was poor on all three berries, no treatment reducing viable counts by >1 log10 unit. In most matrices, prolonging the treatment did not improve the result to any significant degree. The effect was near its plateau after 20 s of treatment. These results provide insight into the effectiveness of UV-C irradiation for inactivating bacterial and viral pathogens and surrogates on fresh and frozen berries having different surface types, under different physical conditions and at different levels of contamination. Overall they show that UV-C as single processing step is unsuitable to inactivate significant numbers of foodborne pathogens on berries.