Oligosaccharides Isolated from MGO™ Manuka Honey Inhibit the Adhesion of Pseudomonas aeruginosa, Escherichia Coli O157:H7 and Staphylococcus Aureus to Human HT-29 cells

peer-reviewedHistorically, honey is known for its anti-bacterial and anti-fungal activities and its use for treatment of wound infections. Although this practice has been in place for millennia, little information exists regarding which manuka honey components contribute to the protective nature of this product. Given that sugar accounts for over 80% of honey and up to 25% of this sugar is composed of oligosaccharides, we have investigated the anti-infective activity of manuka honey oligosaccharides against a range of pathogens. Initially, oligosaccharides were extracted from a commercially-available New Zealand manuka honey—MGO™ Manuka Honey (Manuka Health New Zealand Ltd.)—and characterized by High pH anion exchange chromatography coupled with pulsed amperiometric detection. The adhesion of specific pathogens to the human colonic adenocarcinoma cell line, HT-29, was then assessed in the presence and absence of these oligosaccharides. Manuka honey oligosaccharides significantly reduced the adhesion of Escherichia coli O157:H7 (by 40%), Staphylococcus aureus (by 30%), and Pseudomonas aeruginosa (by 52%) to HT-29 cells. This activity was then proven to be concentration dependent and independent of bacterial killing. This study identifies MGO™ Manuka Honey as a source of anti-infective oligosaccharides for applications in functional foods aimed at lowering the incidence of infectious diseases

Issues in continuous 24-H core body temperature monitoring in humans using an ingestible capsule telemetric sensor

Background: There is increasing interest in the use of pill-sized ingestible capsule telemetric sensors for assessing core body temperature (Tc) as a potential indicator of variability in metabolic efficiency and thrifty metabolic traits. The aim of this study was to investigate the feasibility and accuracy of measuring Tc using the CorTemp® system.Methods: Tc was measured over an average of 20 h in 27 human subjects, with measurements of energy expenditure made in the overnight fasted state at rest, during standardized low-intensity physical activity and after a 600 kcal mixed meal. Validation of accuracy of the capsule sensors was made ex vivo against mercury and electronic thermometers across the physiological range (35–40°C) in morning and afternoon of 2 or 3 consecutive days. Comparisons between capsule sensors and thermometers were made using Bland–Altman analysis. Systematic bias, error, and temperature drift over time were assessed.Results: The circadian Tc profile classically reported in free-living humans was confirmed. Significant increases in Tc (+0.2°C) were found in response to low-power cycling at 40–50 W (~3–4 METs), but no changes in Tc were detectable during low-level isometric leg press exercise (<2 METs) or during the peak postprandial thermogenesis induced by the 600 kcal meal. Issues of particular interest include fast “turbo” gut transit with expulsion time of <15 h after capsule ingestion in one out of every five subjects and sudden erratic readings in teletransmission of Tc. Furthermore, ex vivo validation revealed a substantial mean bias (exceeding ±0.5°C) between the Tc capsule readings and mercury or electronic thermometers in half of the capsules. When examined over 2 or 3 days, the initial bias (small or large) drifted in excess of ±0.5°C in one out of every four capsules.Conclusion: Since Tc is regulated within a very narrow range in the healthy homeotherm’s body (within 1°C), physiological investigations of Tc require great accuracy and precision (better than 0.1°C). Although ingestible capsule methodology appears of great interest for non-invasively monitoring the transit gut temperature, new technology requires a reduction in the inherent error of measurement and elimination of temperature drift and warrants more interlaboratory investigation on the above factors

Low 24-hour core body temperature as a thrifty metabolic trait driving catch-up fat during weight regain after caloric restriction

The recovery of body weight after substantial weight loss or growth retardation is often characterized by a disproportionately higher rate of fat mass vs. lean mass recovery, with this phenomenon of “preferential catch-up fat” being contributed by energy conservation (thrifty) metabolism. To test the hypothesis that a low core body temperature (Tc) constitutes a thrifty metabolic trait underlying the high metabolic efficiency driving catch-up fat, the Anipill system, with telemetry capsules implanted in the peritoneal cavity, was used for continuous monitoring of Tc for several weeks in a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis. In animals housed at 22°C, 24-h Tc was reduced in response to semistarvation (−0.77°C, P < 0.001) and remained significantly lower than in control animals during the catch-up fat phase of refeeding (−0.27°C on average, P < 0.001), the lower Tc during refeeding being more pronounced during the light phase than during the dark phase of the 24-h cycle (−0.30°C vs. −0.23°C, P < 0.01) and with no between-group differences in locomotor activity. A lower 24-h Tc in animals showing catch-up fat was also observed when the housing temperature was raised to 29°C (i.e., at thermoneutrality). The reduced energy cost of homeothermy in response to caloric restriction persists during weight recovery and constitutes a thrifty metabolic trait that contributes to the high metabolic efficiency that underlies the rapid restoration of the body’s fat stores during weight regain, with implications for obesity relapse after therapeutic slimming and the pathophysiology of catch-up growth

Reduced skeletal muscle protein turnover and thyroid hormone metabolism in adaptive thermogenesis that facilitates body fat recovery during weight regain

Objective: The recovery of body composition after weight loss is characterized by an accelerated rate of fat recovery (preferential catch-up fat) resulting partly from an adaptive suppression of thermogenesis. Although the skeletal muscle has been implicated as an effector site for such thrifty (energy conservation) metabolism driving catch-up fat, the underlying mechanisms remain to be elucidated. We test here the hypothesis that this thrifty metabolism driving catch-up fat could reside in a reduced rate of protein turnover (an energetically costly “futile” cycle) and in altered local thyroid hormone metabolism in skeletal muscle.Methods: Using a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis, we measured after 1 week of refeeding in refed and control animals the following: (i) in-vivo rates of protein synthesis in hindlimb skeletal muscles using the flooding dose technique of 13C-labeled valine incorporation in muscle protein, (ii) ex-vivo muscle assay of net formation of thyroid hormone tri-iodothyronine (T3) from precursor hormone thyroxine (T4), and (iii) protein expression of skeletal muscle deiodinases (type 1, 2, and 3).Results: We show that after 1 week of calorie-controlled refeeding, the fractional protein synthesis rate was lower in skeletal muscles of refed animals than in controls (by 30–35%, p < 0.01) despite no between-group differences in the rate of skeletal muscle growth or whole-body protein deposition—thereby underscoring concomitant reductions in both protein synthesis and protein degradation rates in skeletal muscles of refed animals compared to controls. These differences in skeletal muscle protein turnover during catch-up fat were found to be independent of muscle type and fiber composition, and were associated with a slower net formation of muscle T3 from precursor hormone T4, together with increases in muscle protein expression of deiodinases which convert T4 and T3 to inactive forms.Conclusions: These results suggest that diminished skeletal muscle protein turnover, together with altered local muscle metabolism of thyroid hormones leading to diminished intracellular T3 availability, are features of the thrifty metabolism that drives the rapid restoration of the fat reserves during weight regain after caloric restriction

Methylglyoxal: a novel upstream regulator of DNA methylation.

peer reviewed[en] BACKGROUND: Aerobic glycolysis, also known as the Warburg effect, is predominantly upregulated in a variety of solid tumors, including breast cancer. We have previously reported that methylglyoxal (MG), a very reactive by-product of glycolysis, unexpectedly enhanced the metastatic potential in triple negative breast cancer (TNBC) cells. MG and MG-derived glycation products have been associated with various diseases, such as diabetes, neurodegenerative disorders, and cancer. Glyoxalase 1 (GLO1) exerts an anti-glycation defense by detoxifying MG to D-lactate. METHODS: Here, we used our validated model consisting of stable GLO1 depletion to induce MG stress in TNBC cells. Using genome-scale DNA methylation analysis, we report that this condition resulted in DNA hypermethylation in TNBC cells and xenografts. RESULTS: GLO1-depleted breast cancer cells showed elevated expression of DNMT3B methyltransferase and significant loss of metastasis-related tumor suppressor genes, as assessed using integrated analysis of methylome and transcriptome data. Interestingly, MG scavengers revealed to be as potent as typical DNA demethylating agents at triggering the re-expression of representative silenced genes. Importantly, we delineated an epigenomic MG signature that effectively stratified TNBC patients based on survival. CONCLUSION: This study emphasizes the importance of MG oncometabolite, occurring downstream of the Warburg effect, as a novel epigenetic regulator and proposes MG scavengers to reverse altered patterns of gene expression in TNBC

Mécanismes impliqués lors de la récupération musculaire suite à une immobilisation chez le rat

Laboratoire d’accueil Equipe protéolyse, UMR 1019, Unité de Nutrition Humaine Responsable de la spécialité : Didier ATTAIXMasterMuscle wasting leads to a generalized weakening, which results in bed rest, and consequently, contributes to high healthcare costs. Muscle mass is partly controlled by autophagy. Its role during immobilization has been little studied. However, autophagy could play a crucial role during recovery periods following disuse, particularly by eliminating deficient mitochondria by mitophagy. We thus studied the role of autophagy and of mitochondrial alterations in the tibialis anterior muscle after 8 days of immobilization (I8) and 1 to 10 (R1-R10) days of remobilization in comparison with uncasted rats (I0). We have shown that mRNA expression of markers of the initiation of autophagosome formation (ULK1) and of the fusion between autophagosomes with lysosomes (RAB7) decreased in the immobilized and remobilized TA compared to I0, as well as the LC3-II/LC3-I ratio, which reflects the autophagosome formation. We have also shown that immobilization induced a decrease in mRNA expression of markers of mitochondrial biogenesis (PGC1α), of fusion (MFN2, OPA1), fission (MFF) and mitophagy (PINK1) in the TA at I8 and until R6 or R10. Conversely, the protein level of a marker of mitochondrial fission (FIS1) strongly increased in the immobilized and remobilized TA, while those for a marker of mitophagy (PARKIN) increased only in the remobilized TA. Protein levels for a major marker of mitochondrial fission (DRP1) remained unaltered. Finally, mRNA levels for RAB32, involved in DRP1 phosphorylation, increased in the immobilized TA at I8 and until R6. Overall, our data suggest that TA immobilization and remobilization are accompanied with 1) a repression of autophagy, 2) a decrease in mitochondrial biogenesis, 3) alterations of mitochondrial fusion and fission processes that need however to be further investigated, and 4) an alteration of the targeting of deficient mitochondria to mitophagy. Ultimately, this work should contribute to the development of strategies aiming at preventing and/or improving muscle recoveryLa fonte musculaire entraine un affaiblissement généralisé des individus, pouvant conduire à l’alitement, et à terme contribue à élever les coûts de santé publique. La masse musculaire est contrôlée en partie par l’autophagie. Son rôle au cours de l’immobilisation a été peu étudié. Pourtant, l’autophagie pourrait jouer un rôle pendant les phases de récupération suite à l’inactivité musculaire, éventuellement en permettant l’élimination des mitochondries déficientes par mitophagie. Nous avons donc étudié le rôle de l’autophagie et des altérations mitochondriales dans le muscle tibialis anterior (TA) après immobilisation pendant 8 jours (I8) et remobilisation pendant 1 à 10 jours (R1-R10) en comparaison avec des rats non plâtrés (I0). Nous avons montré que l’expression ARNm de marqueurs de l’initiation de la formation des autophagosomes (ULK1) et de la fusion des autophagosomes avec les lysosomes (RAB7) était diminuée dans le TA immobilisé et remobilisé par rapport à I0, de même que le rapport LC3II/LC3I qui témoigne de la formation des autophagosomes. Nous avons également montré que l’immobilisation a réduit des taux d’ARNm de marqueurs de la biogenèse mitochondriale (PGC1 ), de la fusion (MFN2, OPA1), de la fission (MFF), et de la mitophagie (PINK1) dans le TA à I8 et jusqu’à R6 ou R10. Inversement, les niveaux protéiques d’un marqueur de la fission (FIS1) ont fortement augmenté dans le TA immobilisé et remobilisé, alors que ceux d’un marqueur de la mitophagie (PARKIN) ont augmenté uniquement dans le TA remobilisé. Les niveaux protéiques d’un marqueur essentiel à la fission mitochondriale (DRP1) sont restés inchangés. Enfin, les niveaux d’ARNm de RAB32, impliqué dans la phosphorylation de DRP1, ont augmenté dans le TA immobilisé à I8 et jusqu’à R6. L’ensemble de nos données suggèrent que l’immobilisation et la remobilisation du muscle TA sont accompagnées 1) d’une répression de l’autophagie, 2) d’une diminution de la biogenèse mitochondriale, 3) d’altérations des processus de fusion et fission mitochondriales, qu’il sera nécessaire d’approfondir, et 4) d’une altération de l’adressage des mitochondries déficientes vers la mitophagie. Ces travaux devraient permettre à terme le développement ou l’amélioration de stratégies d’intervention visant à prévenir l’atrophie et/ou favoriser la récupératio

Total energy expenditure assessed by doubly labeled water technique and estimates of physical activity in Mauritian children: analysis by gender and ethnicity

In the tropical island of Mauritius, the rise in obesity has accelerated in the past decades, and could be contributed by low physical activity and increased sedentary behavior. The study objectives were to generate the first dataset of total energy expenditure (TEE), to estimate physical activity in Mauritian children, and to explore differences due to gender and ethnicity.Subjects/methods: The doubly labeled water (DLW) technique was used to evaluate TEE over 14 days in 56 Mauritian school children (aged 7–11 years) belonging to the two main ethnic groups: Indian (South Asian descent) and Creole (African/Malagasy descent). Physical activity level (PAL) was calculated as the ratio of TEE and resting energy expenditure (using Schofield equations), and daily step counts were measured by accelerometry. Anthropometry and body composition were also assessed.Results: TEE measured by DLW was lower in Mauritian children (by ~155 kcal/d) than that predicted using FAO/WHO/UNU equations for children of the same sex, age, and body size. Furthermore, TEE, as well as PAL and step counts, also differed according to gender (lower in girls than in boys) and to ethnicity (lower in Indians than in Creoles) even after adjusting for differences in body weight and body composition.Conclusion: These results in Mauritian children provide the first dataset of objectively measured TEE, from which physical activity is estimated as PAL, and complemented by step counts measurements. They suggest potential gender and ethnic differences in TEE and physical activity that need consideration in developing strategies to counter sedentary behavior and obesity

The delayed recovery of the remobilized rat tibialis anterior muscle correlates with sustained increased ubiquitin-proteasome dependent proteolysis and apoptosis, and reflects defects in autophagy and in early regenerative processes

International audienc

Management of mitochondria alterations depends on muscle-specific mechanical constraints during immobilization and recovery

Management of mitochondria alterations depends on muscle-specific mechanical constraints during immobilization and recovery. Fifth International Congress of Translational Research in Human Nutrition (ICTRHN

Mitophagy and mitochondria biogenesis are differentially induced in rat skeletal muscles during immobilization and/or remobilization

Mitochondria alterations are a classical feature of muscle immobilization, and autophagy is required for the elimination of deficient mitochondria (mitophagy) and the maintenance of muscle mass. We focused on the regulation of mitochondrial quality control during immobilization and remobilization in rat gastrocnemius (GA) and tibialis anterior (TA) muscles, which have very different atrophy and recovery kinetics. We studied mitochondrial biogenesis, dynamic, movement along microtubules, and addressing to autophagy. Our data indicated that mitochondria quality control adapted differently to immobilization and remobilization in GA and TA muscles. Data showed i) a disruption of mitochondria dynamic that occurred earlier in the immobilized TA, ii) an overriding role of mitophagy that involved Parkin-dependent and/or independent processes during immobilization in the GA and during remobilization in the TA, and iii) increased mitochondria biogenesis during remobilization in both muscles. This strongly emphasized the need to consider several muscle groups to study the mechanisms involved in muscle atrophy and their ability to recover, in order to provide broad and/or specific clues for the development of strategies to maintain muscle mass and improve the health and quality of life of patients