21 research outputs found

    KHK, PNPLA3 and PPAR as Novel Targets for the Anti-Steatotic Action of Bempedoic Acid

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    Bempedoic acid (BemA) is an ATP-citrate lyase (ACLY) inhibitor used to treat hypercholesterolemia. We studied the anti-steatotic effect of BemA, and the mechanisms involved, in a model of fatty liver in female rats obtained through the administration of a high-fat diet supplemented with liquid fructose (HFHFr) for three months. In the third month, a group of rats was treated with BemA (30 mg/kg/day) by gavage. Plasma analytes, liver histology, adiposity, and the expression of key genes controlling fatty acid metabolism were determined, and PPAR agonism was explored by using luciferase reporter assays. Our results showed that, compared to HFHFr, BemA-treated rats exhibited lower body weight, higher liver/body weight, and reduced hepatic steatosis. In addition to ACLY inhibition, we found three novel mechanisms that could account for the anti-steatotic effect: (1) reduction of liver ketohexokinase, leading to lower fructose intake and reduced de novo lipogenesis; (2) increased expression of patatin-like phospholipase domain-containing protein 3, a protein related to the export of liver triglycerides to blood; and (3) PPARα agonist activity, leading to increased hepatic fatty acid β-oxidation. In conclusion, BemA may represent a novel approach to treat hepatic steatosis, and therefore to avoid progression to advanced stages of non-alcoholic fatty liver disease

    El consumo excesivo de fructosa en el embarazo puede dañar la placenta y provocar estrés oxidativo en los fetos

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    La fructosa se utiliza para fabricar el sirope de maíz rico en fructosa (HFCS, en sus siglas en inglés), el cual se usa para edulcorar gran variedad de alimentos (comidas procesadas, bollería y repostería industrial, helados, mermeladas, salsas y condimentos) y, sobre todo, bebidas o refrescos azucarados. El consumo excesivo de estos alimentos, y por tanto de fructosa, se ha relacionado con la aparición de enfermedades como la obesidad, la diabetes y las enfermedades cardiovasculares [Tappy, 2010]

    CORE DESIGN ACTIVITIES OF THE VERSATILE TEST REACTOR – CONCEPTUAL PHASE

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    The Versatile Test Reactor (VTR) is a new fast spectrum test reactor being developed in the United States under the direction of the US Department of Energy, Office of Nuclear Energy. The VTR mission is to enable accelerated testing of advanced reactor fuels and materials required for advanced reactor technologies. This includes neutron irradiation capabilities which would support alternate coolants including molten salt, lead/lead-bismuth eutectic mixture, gas, and sodium. The VTR aims at addressing most of the needs of the various stakeholders, which is primarily composed of advanced reactor technologists, developers and vendors, as well as a number of others interested parties. Design activities are underway targeting a first criticality date by 2026, with General Electric recently joining the project to contribute to the VTR plant design. Current efforts are focused on all aspects of the VTR design, with the core design being at the center of the initial steps. The VTR is currently proposed as a 300 MWth sodium-cooled fast reactor able to reach peak fast flux levels in excess of 4.0x1015 n/cm2-s (and total flux level of about 6.0x1015 n/cm2-s). In this configuration, it is using ternary metallic fuel with reactor-grade plutonium and 5% low-enriched uranium
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