Potentiel nutraceutique des constituants du babeurre

Les composés mineurs de la membrane du globule de gras laitier (milk fat globule membrane, MFGM) ont été associés à diverses activités biologiques. Le babeurre, en raison de son processus d’obtention, est un produit d’origine laitière particulièrement riche en composés de la MFGM. Cette caractéristique explique l’intérêt grandissant porté à ce sous-produit de la fabrication du beurre, quadruplant le nombre d’articles scientifiques lui étant consacré au cours des 20 dernières années (PubMed). La grande majorité des travaux réalisés jusqu’à aujourd’hui au sujet du babeurre visait à fractionner ou encore à concentrer ses différents constituants, principalement ses phospholipides. Par contre, l’impact biologique de l’ensemble des composantes du babeurre, avant et après digestion, reste encore mal connu. Le but de cette recherche était donc d’évaluer l’impact de l’ensemble des constituants du babeurre sur différents facteurs de risque associés aux maladies cardiovasculaires (CVD). Dans un premier temps, les résultats de cette recherche ont permis de démontrer le potentiel du babeurre frais concentré par microfiltration (MF) à diminuer la solubilité micellaire du cholestérol dans un modèle d’étude in vitro. Ces résultats probants laissaient présager la capacité de certains constituants du babeurre à moduler l’absorption intestinale du cholestérol. Par contre, le fractionnement de ces derniers s’est avéré avoir un impact négatif sur le potentiel d’insolubilisation du cholestérol observé précédemment. Ensuite, les constituants mineurs du babeurre, fort possiblement en raison de ses phospholipides, ont démontré leur capacité à influencer positivement le profil lipidique chez des sujets modérément hypercholestérolémiques lors d’une étude clinique réalisée en chassé-croisé. De plus, lors de cette même étude clinique, la consommation de babeurre, possiblement en résultante de l’action de composantes peptidiques, s’est avérée capable d’abaisser la tension artérielle chez des patients normotendus lorsque comparée à un placebo. Enfin, des peptides issus de l’hydrolyse de babeurre frais (UF) ont démontré un potentiel antioxydant supérieur à ceux obtenus du lactosérum (UF) et du lait écrémé dans un modèle d’étude in vitro. Dans le cadre de l’ensemble des études de ce projet, les différentes activités biologiques se sont avérées peu influencées par l’action des traitements thermiques lorsque les produits subissaient une hydrolyse (p. ex. à la suite de leur consommation). Les résultats de cette étude permettent de mieux comprendre les propriétés bénéfiques du babeurre et ouvrent la voie à une nouvelle utilisation de ce dernier comme ingrédient actif. En effet, ce projet novateur a permis de démontrer le potentiel du babeurre en tant qu’aliment fonctionnel plutôt que comme une source de composés nutraceutiques devant être purifiés ou concentrés. Ainsi, il semble que l’ensemble des constituants du babeurre joue un rôle au niveau des bienfaits observés sur les facteurs de risque de CVD.The minor components in milk fat globule membrane (MFGM) are associated with various biological activities. Buttermilk, owing to its obtainment process, is a milk product particularly rich in MFGM components. This feature accounts for the growing interest in this by-product of the manufacturing of butter. The number of scientific articles dedicated to it has quadrupled in the past 20 years (PubMed). Until today the vast majority of tasks involving buttermilk aimed at either dividing or concentrating its various components, primarily, phospholipids. However, the biological effects of all the components in buttermilk before and after their digestion remains poorly understood. Therefore, the purpose of this research was to evaluate the impact that buttermilk components have on the different risk factors associated with cardiovascular disease (CVD). Initially, the results of in vitro model study revealed that buttermilk freshly concentrated by microfiltration (MF) has the potential to reduce the micellar solubility of cholesterol. These conclusive results presaged the capacity of certain components in buttermilk to regulate the intestinal absorption of cholesterol. Despite, their division proved to have a negative impact on the potential insolubilization of the cholesterol previously observed. Then, in a clinical crossover analysis, minor components of buttermilk - most likely phospholipids - demonstrated a capacity to positively influence the lipid profiles of moderately hypercholesterolemic subjects. Moreover, during this same study, the consumption of buttermilk compared with a placebo proved capable of lowering blood pressure in some patients, possibly resulting from its peptide components. That is to say that, in an in vitro model study, peptides derived from the hydrolysis of fresh buttermilk (UF) demonstrated antioxidant potential superior to those obtained from whey (UF) and skim milk. Within the framework of all studies on this project, various biological activities proved almost uninfluenced by the action of heat treatment when products were hydrolyzed following their consumption. The results of this study allow for a better understanding of the beneficial properties of buttermilk and pave the way for new uses of it as an active ingredient. Indeed, this innovative project has allowed us to demonstrate the potential of buttermilk as a functional food rather than as a source of ingredients needing to undergo a purification or concentration process. In this way, it seems that all components in buttermilk play a role in the observed benefits on risk factors of CVD

Apolipoprotein E isoforms disrupt long-chain fatty acid distribution in the plasma, the liver and the adipose tissue of mice

Evidences suggest that omega-3 fatty acid (n-3 PUFA) metabolism is imbalanced in apolipoprotein E epsilon 4 isoform carriers (APOE4). This study aimed to investigate APOE genotype-dependant modulation of FA profiles, protein and enzyme important to fatty acid (FA) metabolism in the adipose tissue, the liver and the plasma using human APOE-targeted replacement mouse-model (N=37). FA transport (FATP) and binding (FABP) protein levels in tissues and concentrations of liver carnitine palmitoyltransferase 1 (CPT1) were performed. N-3 PUFA concentration was >45% lower in the adipose tissue and liver of APOE4 mice compared to APOE3 mice. In APOE4 mice, there were higher levels of FATP and FABP in the liver and higher FATP in the adipose tissue compared to APOE2 mice. There was a trend towards higher CPT1 concentrations in APOE4 mice compared to APOE3 mice. Therefore, since APOE-isoform differences were not always in line with the unbalanced n-3 PUFA profiles in organs, other proteins may be involved in maintaining n-3 PUFA homeostasis in mice with different APOE-isoforms

Disrupted fatty acid distribution in HDL and LDL according to apolipoprotein E allele

Objectives: Omega-3 polyunsaturated fatty acid (ω-3 PUFA) metabolism seems to be disrupted in carriers of the epsilon 4 allele of apolipoprotein E (E4+). The objective of this study was to investigate whether the ω-3 PUFA distribution in the high and low density lipoproteins is APOE-genotype dependant before and after supplementation with ω-3 PUFAs. Methods: Eighty participants, aged between 20 and 35 y old were recruited and supplemented with 900 mg of eicosapentaenoic acid plus 680 mg of docosahexaenoic acid for 4 wk. Over the 4-wk intervention, blood samples were collected and HDL and LDL particles were obtained using sucrose gradient ultracentifugation. Fatty acid profiles of the HDL and LDL fractions were performed by gas chromatography. Results: Baseline anthropometric characteristics of participants were not significantly different between the two APOE-groups (E4+, N = 10; E4−, N = 70). At baseline, in the LDL of E4+ subjects, the ω-6/ω-3 PUFA ratio was 17% higher than E4− subjects. At week 4, the ω-6/ω-3 PUFA ratio was significantly higher in the LDL of E4+ than E4− subjects. There was a significant genotype × time interaction for 16:0 in HDL and LDL and for 18:2 ω-6 in HDL. DHA in the HDL was positively correlated to HDL-C levels pre- and postsupplementation in E4− only. Conclusions: Contrary to what we anticipated, ω-3 PUFAs content? in HDL and LDL were not APOE isoform-dependant in young participants. However, young E4+ participants already had a tendency toward lower baseline-DHA levels in LDL particles as well as a more atherogenic ω-6/ω-3 PUFA ratio in LDL pre- and post-supplementatio

Postprandial enrichment of triacylglycerol-rich lipoproteins with omega-3 fatty acids: lack of an interaction with apolipoprotein E genotype?

Background We have previously demonstrated that carrying the apolipoprotein (apo) E epsilon 4 (E4+) genotype disrupts omega-3 fatty acids (n − 3 PUFA) metabolism. Here we hypothesise that the postprandial clearance of n − 3 PUFA from the circulation is faster in E4+ compared to non-carriers (E4−). The objective of the study was to investigate the fasted and postprandial fatty acid (FA) profile of triacylglycerol-rich lipoprotein (TRL) fractions: Sf >400 (predominately chylomicron CM), Sf 60 − 400 (VLDL1), and Sf 20 − 60 (VLDL2) according to APOE genotype. Methods Postprandial TRL fractions were obtained in 11 E4+ (ϵ3/ϵ4) and 12 E4− (ϵ3/ϵ3) male from the SATgenϵ study following high saturated fat diet + 3.45 g/d of docosahexaenoic acid (DHA) for 8-wk. Blood samples were taken at fasting and 5-h after consuming a test-meal representative of the dietary intervention. FA were characterized by gas chromatography. Results At fasting, there was a 2-fold higher ratio of eicosapentaenoic acid (EPA) to arachidonic acid (P = 0.046) as well as a trend towards higher relative% of EPA (P = 0.063) in the Sf >400 fraction of E4+. Total n − 3 PUFA in the Sf 60 − 400 and Sf 20 − 60 fractions were not APOE genotype dependant. At 5 h, there was a trend towards a time × genotype interaction (P = 0.081) for EPA in the Sf >400 fraction. When sub-groups were form based on the level of EPA at baseline within the Sf >400 fraction, postprandial EPA (%) was significantly reduced only in the high-EPA group. EPA at baseline significantly predicted the postprandial response in EPA only in E4+ subjects (R2 = 0.816). Conclusion Despite the DHA supplement contain very low levels of EPA, E4+ subjects with high EPA at fasting potentially have disrupted postprandial n − 3 PUFA metabolism after receiving a high-dose of DHA

Genetic Contributions to the Association between Adult Height and Head and Neck Cancer : A Mendelian Randomization Analysis

Acknowledgements: The authors thank the Italian Association for Research on Cancer (AIRC, IG 2013 n. 14211) and the PRECeDI project (Marie Skłodowska-Curie Research and Innovation Staff Exchange - RISE N°645740) for supporting the work of Roberta Pastorino and Anna Puggina.Peer reviewedPublisher PD

A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer

© The Author 2015. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] Funding This work was supported the National Institutes of Health (R01CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116). Notes The authors thank all of the participants who took part in this research and the funders and technical staff who made this study possible. We acknowledge and thank Simone Benhamou (INSERM, France) for sample contributions. We also acknowledge and thank The Cancer Genome Atlas initiative, whose data contributed heavily to this study.Peer reviewedPublisher PD

The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract

Acknowledgments: The authors thank all of the participants who took part in this research and the funders and support and technical staff who made this study possible. We also acknowledge and thank The Cancer Genome Atlas initiative whose data contributed heavily to this study. Funding: Funding for study coordination, genotyping of replication studies and statistical analysis was provided by the US National Institutes of Health (R01 CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 x 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 x 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 x 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers

Effect of cream pasteurization, microfiltration and enzymatic proteolysis on in vitro cholesterol-lowering activity of buttermilk solids

The lipids and proteins of buttermilk solids have been associated with several potential health benefits. In this work, the effect of cream pasteurization, microfiltration (MF) and enzymatic proteolysis on the chemical composition and cholesterol-lowering activity of buttermilk solids was studied. Buttermilk was made from pasteurized or unpasteurized cream and fractionated using a 0.5-μm MF membrane or treated with pepsin or pepsin followed by trypsin. The cholesterol-lowering activity of the products obtained was measured as micellar solubility of cholesterol in vitro. This value was reduced significantly by 57.1% of the control in the presence of raw-cream buttermilk, while buttermilk from pasteurized cream had a much lower impact (reduction of 17.0%). These results suggest a strong inhibitory effect of components in raw-cream buttermilk on in vitro micellar solubility of cholesterol. MF retentate and permeate of buttermilks made from either cream had smaller effects on micellar solubility. Enzymatic hydrolysis of buttermilk made from pasteurized cream seemed to restore the lost cholesterol-lowering activity