Impact of Gut Microbiota on Host Glycemic Control

Given that obesity and associated disorder type II diabetes mellitus have reached epidemic proportions worldwide, the development of efficient prevention and therapeutic interventions is a global public health interest. There is now a large body of evidence suggesting that the micro-organisms colonizing the human gut, known as gut microbiota, play a central role in human physiology and metabolism. Understanding how gut microbiota affects and regulates key metabolic functions such as glucose regulation and insulin resistance is an important health issue. The present review summarizes recent advances in our understanding of how gut bacterial species interfere with host metabolic phenotype. We will examine key biological molecular mechanisms underlying the impact of gut microbiota on host glycemic control including: incretin secretion, short-chain fatty acid production, bile acid metabolism, and adipose tissue regulation. We will highlight how prebiotic/probiotic interventions affect these bacterial processes and are now considered as promising approaches to treat obese and diabetic patients

Interaction of mannose-6-phosphate with the hysteretic transition in glucose-6-phosphate hydrolysis in intact liver microsomes

AbstractWe showed previously that glucose-6-phosphatase activity was characterised in intact liver microsomes by a hysteretic transition between a rapid and a slower catalytic form of the enzyme. We have now further investigated the substrate specificity of these two kinetic forms. It was found that the pre-incubation of intact microsomes with mannose-6-phosphate or glucose-6-phosphate (50 μM for 30 s) suppressed the burst in glucose-6-phosphatase activity, that the hysteretic transition was reversible and that mannose-6-phosphate inhibited glucose-6-phosphate hydrolysis during the first seconds of incubation, but not anymore after the burst. Our results indicate (i) that mannose-6-phosphate is recognised by the enzyme and can promote the hysteretic transition and (ii) that the transient phase is part of the catalytic mechanism itself

Environmental Pollutants and Metabolic Disorders: The Multi-Exposure Scenario of Life

Obesity and diabetes have reached epidemic proportions the past few decades and continue to progress worldwide with no clear sign of decline of the epidemic. Obesity is of high concern because it is the main risk factor for a number of non-communicable diseases such as cardiovascular diseases and type 2 diabetes. Metabolic diseases constitute a major challenge as they are associated with an overall reduced quality of life and impose a heavy economic burden on countries. These are multifactorial diseases and it is now recognized that environmental exposure to man-made chemical pollutants is part of the equation. Yet, risk assessment procedures are based on a one-by-one chemical evaluation which does not meet the specificities of the multi-exposure scenario of life, e.g., a combined and long-term exposure to even the smallest amounts of chemicals. Indeed, it is assumed that environmental exposure to chemicals will be negligible based on the low potency of each chemical and that they do not interact. Within this mini-review, strong evidences are brought that exposure to low levels of multiple chemicals especially those shown to interfere with hormonal action, the so-called endocrine disrupting compounds do trigger metabolic disturbances in conditions in which no effect was expected if considering the concentration of each individual chemical in the mixture. This is known as the cocktail effect. It means that risk assessment procedures are not protective enough and thus that it should be revisited for the sake of Public Health

FUSE observations towards the pole-on Be star HR 5223

New spectra have been obtained for the pole-on Be star HR 5223 (HD 120991) using the Far Ultraviolet Satellite Explorer (FUSE). We give a complete description of the far-UV spectral range (920 to 1180 Å). The spectra are affected by strong blends with interstellar lines and molecular bands that also significantly lower the energy distribution of the star. We produce a synthetic spectrum of the interstellar medium (ISM) to determine the column densities of several elements (H2, H I, N I, O I ...) seen towards HR 5223 and to disentangle the components due to the ISM, the photosphere and/or to the circumstellar envelope. The line identification list is available at the CDS. Using the obtained column densities, we determine the reddening of the star due to the ISM only and locate the star relative to the nearby IS clouds. The fit of the dereddened UV flux distribution with models that account for the gravitational darkening due to the stellar fast rotation allowed us to estimate the stellar fundamental parameters (Teff = 22 000 K; log g = 3.7) and its distance (d = 834 ± 20 pc). The distance obtained, which has to be considered as the most accurate available at the moment, is in agreement with the characteristics of the ISM matter distribution that affects the observed spectrum of the star and with the detecting limits of the HIPPARCOS satellite.Facultad de Ciencias Astronómicas y Geofísica

Abdominal adipocyte populations in women with visceral obesity

Visceral obesity is independently related to numerous cardiometabolic alterations, with adipose tissue dysfunction as a central feature. Objective: To examine whether omental (OM) and subcutaneous (SC) adipocyte size populations in women relate to visceral obesity, cardiometabolic risk factors and adipocyte lipolysis independent of total adiposity. Design and Methods: OM and SC fat samples were obtained during gynecological surgery in 60 women [mean age: 46.1±5.9 years; mean BMI: 27.1±4.5 kg/m2 (range: 20.3-41.1 kg/m2)]. Fresh samples were treated with osmium tetroxide and were analyzed with a Multisizer Coulter. Cell size distributions were computed for each sample with exponential and Gaussian function fits. Results: Computed tomography-measured visceral fat accumulation was the best predictor of larger cell populations as well as the percentage of small cells in both OM and SC fat (p<0.0000 for all). Accordingly, women with visceral obesity had larger cells in the main population and higher proportion of small adipocytes independent of total adiposity (p≤0.05). Using linear regression analysis, we found that women characterized by larger-than-predicted adipocytes in either OM or SC adipose tissue presented higher visceral adipose tissue area, increased percentage of small cells and HOMAir index as well as higher OM adipocyte isoproterenol-, forskolin- and dibutyryl cAMP- stimulated lipolysis compared to women with smaller-than predicted adipocytes, independent of total adiposity (p≤0.05). Conclusion: Excess visceral adipose tissue accumulation is a strong marker of both adipocyte hypertrophy and increased number of small cells in either fat compartment, which relates to higher insulin resistance index and lipolytic response, independent of total adiposity

Revaluación del modelo geológico del campo tello (valle superior del magdalena) y sus implicaciones en el programa de desarrollo

The Tello field reservoir section was interpreted from 3-D seismic and biostratigraphic analysis from cuttings as an Early Miocene blanket-like fluvial sandstone overlying an Oligocene unconformity. Reservoir stratigraphy was "layer cake". Absence of sandstone in wells was interpreted as a lateral facies change to mudstone. Unexpected results from a recent infill drilling and water injection led to a review of the geological model.  Data from over 800 feet of outcrop, 928 feet of cores from five wells, 21 new biostratigraphic analysis from cores, dipmeter and wireline logs from 35 wells, 5 check-shot and a 36 km2 seismic cube were interpreted and integrated to define a new reservoir model. Sedimentological studies indicate that the reservoir section was deposited in a well oxygenated, current-swept, shallow-marine shelf as agradational tidally influenced cycles, as progradational shorefaces and as tidal bars and channels. High-resolution sequence stratigraphic subdivision of the reservoir allows identification of repeated sections in several wells. Dipmeter data shows low to very high dip angles within the oil-bearing reservoir and confirms the location of low-angle thrust faults, interpreted from well log correlations. The Tello field consists of 5 thrust sheets arranged as a series of partly overlapping ramp anticlines with high-angle dipping backlimbs and low-angle forelimbs. Structural horses involve mostly Monserrate strata. Siliceous siltstones in the Lower Monserrate and Upper Villeta formations act as detachment surfaces for these thrusts. The three easternmost sheets form an antiformal stack that shares the same trailing branch point. Although the roof sequence has been eroded by the Miocene unconformity, the small vertical offset (forelimb against the footwall flat) at the lowest fault-bend indicates that the "Roof sequence" was nearby. By the contrary, the western thrust faults cut the roof sequence as the break-back sequence of deformation occurred. These events are the result of cumulative episodes of deformation and thrust reactivation. Folding of the unconformity and the Miocene strata and the better preservation of the Monserrate strata in the structurally high positions f the field supports reactivation of the westernmost faults. Integration of multiple data sets lead to a reinterpretation of the stratigraphic and structural models that results in better reservoir modeling and planning and recognition of undrilled potential of the Tello field. Estimated new additional oil reserves are about 18 MMBbls. The last 7 wells honored the new reservoir model and daily oil production has increased 80 %.EI Campo Tello, localizado en el Valle Superior del Magdalena, ha producido aproximadamente 60 millones de barriles de aceite durante 26 años. En estudios anteriores, la sección productora del campo era interpretada como areniscas fluviales del Mioceno Temprano que suprayacen la discordancia del Oligoceno. Se asumía la zona productora como horizontal y la ausencia de arenas era interpretada como cambios laterales de facies a lodolitas. Con el objetivo de diseñar un plan de desarrollo para el campo se decidió reevaluar los modelos geológico y de yacimientos con todos los datos disponibles. Esta revisión condujo a modificaciones muy importantes en los modelos y en la estrategia de desarrollo del campo.  En el área de Geología, estudios sedimentológicos indican que la sección productora fue depositada en una plataforma marina somera inyección de agua. Con estos proyectos se estima incrementar las reservas recuperables de aceite en aproximadamente 26 millones de barriles. A Diciembre de 2000 se obtuvieron tasas promedio de más de 14.000 BAPD (barriles de aceite por día). 9000 barriles más de lo que producía el campo al inicio de este estudio

TNF-α- and tumor-induced skeletal muscle atrophy involves sphingolipid metabolism

Additional filesInternational audienceUNLABELLED: ABSTRACT: BACKGROUND: Muscle atrophy associated with various pathophysiological conditions represents a major health problem, because of its contribution to the deterioration of patient status and its effect on mortality. Although the involvement of pro-inflammatory cytokines in this process is well recognized, the role of sphingolipid metabolism alterations induced by the cytokines has received little attention. RESULTS: We addressed this question both in vitro using differentiated myotubes treated with TNF-α, and in vivo in a murine model of tumor-induced cachexia. Myotube atrophy induced by TNF-α was accompanied by a substantial increase in cell ceramide levels, and could be mimicked by the addition of exogenous ceramides. It could be prevented by the addition of ceramide-synthesis inhibitors that targeted either the de novo pathway (myriocin), or the sphingomyelinases (GW4869 and 3-O-methylsphingomyelin). In the presence of TNF-α, ceramide-synthesis inhibitors significantly increased protein synthesis and decreased proteolysis. In parallel, they lowered the expression of both the Atrogin-1 and LC3b genes, involved in muscle protein degradation by proteasome and in autophagic proteolysis, respectively, and increased the proportion of inactive, phosphorylated Foxo3 transcription factor. Furthermore, these inhibitors increased the expression and/or phosphorylation levels of key factors regulating protein metabolism, including phospholipase D, an activator of mammalian target of rapamycin (mTOR), and the mTOR substrates S6K1 and Akt. In vivo, C26 carcinoma implantation induced a substantial increase in muscle ceramide, together with drastic muscle atrophy. Treatment of the animals with myriocin reduced the expression of the atrogenes Foxo3 and Atrogin-1, and partially protected muscle tissue from atrophy. CONCLUSIONS: Ceramide accumulation induced by TNF-α or tumor development participates in the mechanism of muscle-cell atrophy, and sphingolipid metabolism is a logical target for pharmacological or nutritional interventions aiming at preserving muscle mass in pathological situations

The microRNA Signature in Response to Insulin Reveals Its Implication in the Transcriptional Action of Insulin in Human Skeletal Muscle and the Role of a Sterol Regulatory Element–Binding Protein-1c/Myocyte Enhancer Factor 2C Pathway

International audienceOBJECTIVE: Factors governing microRNA expressions in response to changes of cellular environment are still largely unknown. Our aim was to determine whether insulin, the major hormone controlling whole-body energy homeostasis, is involved in the regulation of microRNA expressions in human skeletal muscle. RESEARCH DESIGN AND METHODS: We carried out comparative microRNA (miRNA) expression profiles in human skeletal muscle biopsies before and after a 3-h euglycemic-hyperinsulinemic clamp, with TaqMan low-density arrays. Then, using DNA microarrays, we determined the response to insulin of the miRNA putative target genes in order to determine their role in the transcriptional action of insulin. We further characterized the mechanism of action of insulin on two representative miRNAs, miR-1 and miR-133a, in human muscle cells. RESULTS: Insulin downregulated the expressions of 39 distinct miRNAs in human skeletal muscle. Their potential target mRNAs coded for proteins that were mainly involved in insulin signaling and ubiquitination-mediated proteolysis. Bioinformatic analysis suggested that combinations of different downregulated miRNAs worked in concert to regulate gene expressions in response to insulin. We further demonstrated that sterol regulatory element-binding protein (SREBP)-1c and myocyte enhancer factor 2C were involved in the effect of insulin on miR-1 and miR-133a expression. Interestingly, we found an impaired regulation of miRNAs by insulin in the skeletal muscle of type 2 diabetic patients, likely as consequences of altered SREBP-1c activation. CONCLUSIONS: This work demonstrates a new role of insulin in the regulation of miRNAs in human skeletal muscle and suggests a possible implication of these new modulators in insulin resistance

Effects of gravitational darkening on the determination of fundamental parameters in fast rotating B-type stars

In this paper we develop a calculation code to account for the effects carried by fast rotation on the observed spectra of early-type stars. Stars are assumed to be in rigid rotation and the grid of plane-parallel model atmospheres used to represent the gravitational darkening are calculated by means of a non-LTE approach. Attention is paid on the relation between the apparent and parent non-rotating counterpart stellar fundamental parameters and apparent and true vsini parameters as a function of the rotation rate Omega/Omega_c, stellar mass and inclination angle. It is shown that omission of gravitational darkening in the analysis of chemical abundances of CNO elements can produce systematic overestimation or underestimation, depending on the lines used, rotational rate and inclination angle. The proximity of Be stars to the critical rotation is re-discussed by correcting not only the vsini of 130 Be stars, but also their effective temperature and gravity to account for stellar rotationally induced geometrical distortion and for the concomitant gravitational darkening effect. We concluded that the increase of the vsini estimate is accompanied by an even higher value of the stellar equatorial critical velocity, so that the most probable average rate of angular velocity of Be stars attains Omega/Omega_c ~ 0.88.Comment: 20 pages, 16 figures. Submitted for publication in A&