Metabolic Functions of Peroxisome Proliferator-Activated Receptor β/δ in Skeletal Muscle

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that act as lipid sensors and adapt the metabolic rates of various tissues to the concentration of dietary lipids. PPARs are pharmacological targets for the treatment of metabolic disorders. PPARα and PPARγ are activated by hypolipidemic and insulin-sensitizer compounds, such as fibrates and thiazolidinediones. The roles of PPARβ/δ in metabolic regulations remained unclear until recently. Treatment of obese monkeys and rodents by specific PPARβ/δ agonists promoted normalization of metabolic parameters and reduction of adiposity. Recent evidences strongly suggested that some of these beneficial actions are related to activation of fatty acid catabolism in skeletal muscle and also that PPARβ/δ is involved in the adaptive responses of skeletal muscle to environmental changes, such as long-term fasting or physical exercise, by controlling the number of oxidative myofibers. These observations indicated that PPARβ/δ agonists might have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption in skeletal muscle and reducing obesity

Les intoxications au paracétamol

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Allergie et environnement

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Étude des rôles physiologiques du récepteur nucléaire "Peroxisome Proliferator-Activated Receptor ß " dans le muscle squelettique (protéine relais de l'activité physique)

Obésité et diabète se développent dans de nombreux pays, en raison d'une alimentation enrichie en graisses et d'un manque d'exercice physique. Les lipides, présents en trop grande quantité dans l'organisme ne sont plus suffisamment métabolisés. Afin d'améliorer leur catabolisme musculaire, l'attention a été portée sur une famille de récepteurs nucléaires, les PPARs, et notamment sur l'isoforme beta, très exprimé dans les tissus à fort métabolisme lipidique (cœur et muscle squelettique). Il contrôle l'expression de gènes impliqués dans le catabolisme des acides gras in vitro. La construction d'un modèle transgénique murin de surexpression musculaire de PPARbeta, ainsi que l'utilisation d'un agoniste spécifique ont permis de révéler ses effets sur la physiologie musculaire. La surexpression de PPARbeta induit un remodelage musculaire caractérisé par une forte hyperplasie des fibres oxydatives et une angiogénèse massive. Son activation pharmacologique conduit au même phénotype, avec des effets nettement plus rapides. Ce remodelage est similaire à celui induit par l'exercice d'endurance. Parmi les nombreuses voies de signalisation impliquées, celles du VEGF, de la p38 kinase et de la calcineurine semblent directement contrôlées par PPARbeta. De plus, la surexpression ou l'activation de PPARbeta protègent contre le développement d'une obésité induite par une alimentation hypercalorique. Le flux lipidique sanguin est redirigé vers le muscle, menant à une réduction de la taille des adipocytes. PPARbeta régule donc les capacités oxydatives et le développement du muscle, et constitue une cible pharmacologique pour lutter contre l'obésité et les dégénérescences musculaires.NICE-BU Sciences (060882101) / SudocSudocFranceF

This ped is my ped: Visual separation and near infrared spectra allow determination of the origins of soil macroaggregates

International audienceMacroaggregation is a highly dynamic attribute of soils that is claimed to have a significant impact on their ability to store C and conserve nutrients. A major obstacle to the description and modelling of macroaggregate dynamics, and of the associated processes, is an almost complete ignorance of the real origin of the different types of aggregates found in soils, their turnover times and positions in the soil matrix. We present here a general methodological approach in which the origin of aggregates separated according to visual criteria could be determined by comparing their specific organic matter signatures assessed by Near Infrared Spectrometry (NIRS) to signatures of biogenic structures produced by soil ecosystem engineers (invertebrates and roots) living in the same soil. Macroaggregates and other soil components were separated visually from samples taken at 61 locations regularly distributed across a watershed in Nicaragua and representing crops, pastures, forests, coffee plantations and fallows. Coinertia analyses among soil macroinvertebrate communities and the matrix of soil morphological variables showed highly significant relationships. In Amazonian forest patches and pastures from the state of Pará in Brazil, 75 different types of biogenic structures were collected at the soil surface and on tree trunks, and analysed by the NIRS spectral method. Significant differences among the different types of structures allowed grouping according to their broad phylogenetic origin with large interspecifc differences. In a field experiment conducted at the same site, soils previously under pastures were planted in 16 possible combinations of four plant species, in a fully randomized design replicated three times in different sites. Surface casts of the earthworm species Andiodrilus pachoensis and soil macroaggregates separated by our visual technique had significantly different spectral signatures depending on the location of the plot and the composition of plant cover. However, the comparison of NIRS signatures of soil macroaggregates and casts suggested that Andiodrilus pachoensis was not responsible for the production of the biogenic aggregates that comprised a large proportion on the soil volume in this soil

High Content Screening Using New U2OS Reporter Cell Models Identifies Harmol Hydrochloride as a Selective and Competitive Antagonist of the Androgen Receptor

International audienc

Current diagnostic and clinical issues of screening for dihydropyrimidine dehydrogenase deficiency

International audienc

Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency

International audienceAIMS: Determining dihydropyrimidine dehydrogenase (DPD) activity by measuring patient’s uracil (U) plasma concentration is mandatory before fluoropyrimidines (FP) administration in France. In this study, we aimed to refine the pre-analytical recommendations for determining U and dihydrouracil (UH(2) ) concentrations, since they are essential in reliable DPD deficiency testing. METHODS: U and UH(2) concentrations were collected from 14 hospital laboratories. Stability in whole blood and plasma after centrifugation, the type of anticoagulant and long-term plasma storage were evaluated. The variation induced by time and temperature was calculated and compared to an acceptability range of ± 20%. Inter-occasion variability (IOV) of U and UH(2) was assessed in 573 patients double sampled for DPD-deficiency testing. RESULTS: Storage of blood samples before centrifugation at room temperature (RT) should not exceed 1 h, whereas cold (+4°C) storage maintains U stable after 5 hours. For patients correctly double sampled, IOV of U reached 22.4% for U (SD = 17.9%, range = [0-99%]). Notably, 17% of them were assigned with a different phenotype (normal or DPD deficient) based on the analysis of their two samples. For those having at least one non-compliant sample, this percentage increased up to 33.8%. The moment of blood collection did not affect the DPD phenotyping result. CONCLUSION: Caution should be taken when interpreting U concentrations if the time before centrifugation exceeds 1 h at RT, since it rises significantly afterwards. Not respecting the pre-analytical conditions for DPD phenotyping increases the risk of DPD status misclassification