Updated survey of the steroid-converting enzymes in human adipose tissues

Over the past decade, adipose tissues have been increasingly known for their endocrine properties, that is, their ability to secrete a number of adipocytokines that may exert local and/or systemic effects. In addition to these hormonal peptides, adipose tissues have long been recognized as significant sites for steroid hormone transformation and action. We hereby provide an updated survey of the many steroid-converting enzymes that may be detected in human adipose tissues, their activities and potential roles. In addition to the now well-established role of aromatase and 11β-hydroxysteroid dehydrogenase (HSD) type 1, many enzymes have been reported in adipocyte cell lines, isolated mature cells and/or preadipocytes. These include 11βHSD type 2, 17β-HSDs, 3β-HSD, 5α-reductases, sulfatases and glucuronosyltransferases. Some of these enzymes are postulated to bear relevance for adipose tissue physiology and perhaps for the pathophysiology of obesity. This elaborate set of steroid-converting enzymes in the cell types of adipose tissue deserves further scientific attention. Our work on 20α-HSD (AKR1C1), 3αHSD type 3 (AKR1C2) and 17β-HSD type 5 (AKR1C3) allowed us to clarify the relevance of these enzymes for some aspects of adipose tissue function. For example, AKR1C2 expression down-regulation in preadipocytes seems to potentiate the inhibitory action of dihydrotestosterone on adipogenesis in this model. Many additional studies are warranted to assess the impact of intra-adipose steroid hormone conversions on adipose tissue functions and chronic conditions such as obesity, diabetes and cancer

17β-HSD type 2 activity and localization in human adipose tissue

Testosterone can be converted into androstenedione (4-dione) by 17β-hydroxysteroid dehydrogenase (HSD) activity likely performed by 17β-HSD type 2. Our objective was to evaluate the rate of testosterone conversion to 4-dione as well as expression and localization of 17β-HSD type 2 in omental (OM) vs. subcutaneous (SC) adipose tissues of men. Formation of 4-dione from testosterone was significantly higher in homogenates (p ≤ 0.001) and explants (p ≤ 0.01) of OM than SC tissue. Microscopy analyses and biochemical assays in cell fractions localized the enzyme in the vasculature/endothelial cells of adipose tissues. Conversion of testosterone to 4-dione was weakly detected in most OM and/or SC preadipocyte cultures. Positive correlations were found between 17β-HSD type 2 activity in whole tissue and BMI or SC adipocyte diameter. We conclude that conversion of testosterone to 4-dione detected in abdominal adipose tissue is caused by 17β-HSD type 2 which is localized in the vasculature of the adipose compartment

Identification de biomarqueurs du syndrome métabolique par une approche métabolomique chez l'humain

Les profils métabolomiques d’acides aminés (AA) sanguins d’individus obèses présentent des niveaux élevés d’acides aminés à chaîne ramifiée (AACR) possiblement en lien avec une altération des enzymes de leur catabolisme dans le tissu adipeux. Nous avons étudié les profils d’AA sanguins associés à l’obésité viscérale et aux facteurs de risque cardiométabolique ainsi que l’expression des gènes et l’abondance protéique des enzymes du catabolisme des AACR dans les tissus adipeux d’un échantillon de femmes ayant divers degrés d’adiposité. Nous avons démontré que les femmes obèses présentaient des niveaux d’AACR, de glutamate et de tyrosine augmentés. De plus, les taux circulants d’AACR étaient associés positivement aux marqueurs d’homéostasie du glucose et d’adiposité totale et sous-cutanée tandis que le glutamate et l’acylcarnitine C3 étaient associés positivement à l’aire de tissu adipeux viscéral et aux niveaux de triglycérides sanguins. L’expression et l’abondance protéique des enzymes du catabolisme des AACR étaient abaissées dans le tissu adipeux omental des femmes obèses. Les résultats de cette étude suggèrent que les concentrations sanguines d’AACR, de tyrosine et de glutamate sont plus élevées chez les individus obèses. Cette élévation des taux plasmatiques pourrait être associée à une diminution de l’expression et de l’abondance protéique des enzymes responsables du catabolisme des AACR, principalement observée dans les tissus adipeux omentaux des individus obèses.Metabolomic profiling of obese individuals revealed high blood levels of branched-chain amino acids (BCAA) possibly linked to altered adipose tissue BCAA catabolism. We examined plasmatic AA profiling linked with visceral obesity and cardiometabolic risk factors as well as gene expression and protein abundance of BCAA-catabolizing enzymes in adipose tissue of lean-to-obese women. We showed that obese women had significantly higher circulating BCAA, glutamate and tyrosine levels. Moreover, circulating BCAA levels were positively related to glucose homeostasis variables in addition to total and subcutaneous adiposity markers while glutamate and C3 acylcarnitine levels were positively associated with visceral adipose tissue area and triglycerides. Obese women had lower expression and protein levels of BCAA-catabolizing enzymes in visceral adipose tissue specifically. The results of this study suggest that plasma concentrations of BCAA, tyrosine and glutamate are elevated in obese individuals. This could be associated with a reduction in expression and protein abundance of BCAA-catabolizing enzymes mainly observed in omental adipose tissue of obese individuals

Construction et évaluation d'un modèle d'élaboration de la base de données pour un système d'enseignement assisté par ordinateur

Québec Université Laval, Bibliothèque 201

Le travail personnel encadré des lycéens

Through a dozen of teachers’recorded words that we have taken down for both last years, compared with those of the ten pupils’teams we met during the year 2000, the issue of this paper will be to investigate on the reality of boys’and girls’working at the secondary school (17-19 years old), whithin the framework of a new educational device paradoxically called «managed personal works » . While bringing out the misunderstanding which, as for us, characterize the hard running of this device, the purpose is also to show some interesting changes in the relation to knowledge and school work, owing to the actually produced works.Le propos de cet article, à travers les paroles d’une douzaine d’enseignants rencontrés au cours des deux dernières années, confrontées à celles d’une dizaine de groupes d’élèves de classe de première, rencontrés dès l’année 2000, sera d’enquêter sur la réalité du travail des lycéens, dans le cadre du nouveau dispositif pédagogique original et paradoxal des «travaux personnels encadrés » . Tout en mettant en lumière les malentendus qui caractérisent, selon nous, le fonctionnement difficile du dispositif, il s’agit de montrer aussi quelques transformations intéressantes du rapport au savoir et au travail scolaire, à la faveur des travaux effectivement réalisés.Boulet Marie-Hélène, Delattre Joëlle, Sagot Michèle. Le travail personnel encadré des lycéens. In: Spirale. Revue de recherches en éducation, n°33, 2004. Pour une approche plurielle du travail scolaire : élèves et étudiants, sous la direction de Anne Barrère. pp. 53-69

Alterations of endogenous sphingolipid metabolism in cardiometabolic diseases: towards novel therapeutic approaches

International audienceThe increasing prevalence of obesity and metabolic diseases is a worldwide public health concern, and the advent of new analytical technologies has made it possible to highlight the involvement of some molecules, such as sphingolipids (SL), in their pathophysiology. SL are constituents of cell membranes, lipoproteins and lipid droplets (LD), and are now considered as bioactive molecules. Indeed, growing evidence suggests that SL, characterized by diverse families and species, could represent one of the main regulators of lipid metabolism. There is an increasing amount of data reporting that plasma SL profile is altered in metabolic diseases. However, less is known about SL metabolism dysfunction in cells and tissues and how it may impact the lipoprotein metabolism, its functionality and composition. In car-diometabolic pathologies, the link between serum SL concentrations and alterations of their metabolism in various organs and LD is still unclear. Pharmacological approaches have been developed in order to activate or inhibit specific key enzymes of the SL metabolism, and to positively modulate SL profile or related metabolic pathways. Nevertheless, little is known about the long-term impact of such approaches in humans and the current literature still focuses on the decomposition of the different parts of this complex system rather than performing an integrated analysis of the whole SL metabolism. In addition, since SL can be provided from exogenous sources, it is also of interest to evaluate their impact on the homeostasis of endogenous SL metabolism, which could be beneficial in prevention or treatment of obesity and related metabolic disorders