3,5-Diiodo-L-Thyronine Modifies the Lipid Droplet Composition in a Model of Hepatosteatosis

Background/Aims: Fatty acids are the main energy stores and the major membrane components of the cells. In the hepatocyte, fatty acids are esterified to triacylglycerols (TAGs) and stored in lipid droplets (LDs). The lipid lowering action of 3,5-diiodo-L-thyronine (T 2 ) on an in vitro model of hepatosteatosis was investigated in terms of fatty acid and protein content of LDs, lipid oxidation and secretion. Methods: FaO cells were exposed to oleate/ palmitate, then treated with T 2 . Results: T 2 reduced number and size of LDs, and modified their acyl composition by decreasing the content of saturated (SFA) vs monounsaturated (MUFA) fatty acids thus reversing the SFA/MUFA ratio. The expression of the LD-associated proteins adipose differentiation-related protein (ADRP), oxidative tissue-enriched PAT protein (OXPAT), and adipose triglyceride lipase (ATGL) was increased in 'steatotic' cells and further up-regulated by T 2 . Moreover, T 2 stimulated the mitochondrial oxidation by up-regulating carnitine-palmitoyl-transferase (CPT1), uncoupling protein 2 (UCP2) and very long-chain acylcoenzyme A dehydrogenase (VLCAD). Conclusions: T 2 leads to mobilization of TAGs from LDs and stimulates mitochondrial oxidative metabolism of fatty acids, in particular of SFAs, and thus enriches of MUFAs the LDs. This action may protect the hepatocyte from excess of SFAs that are more toxic than MUFAs

use of an in vitro model of hepatic steatosis for studying the anti oxidant and antisteatotic effects of fucoidan polysaccharides

Non Alcoholic Fatty Liver Disease (NAFLD) is characterised by fat accumulation in hepatocytes in the form of triacyglycerols (TAGs) within cytosolic lipid droplets. Fucoidans (FUs) are biologically active polysaccharides usually isolated from brown marine algae, but recently identified also in terrestrial plants. In this study, we aimed to investigate the anti-oxidant and anti-steatotic effects of FUs purified from C. compressa, F. hermonis, and E. globulus. To this aim, we used a validated NAFLD in vitro model consisting of rat hepatoma FaO cells exposed to an oleate/palmitate mixture. Such a model is suitable for rapid investigation of direct effects of natural and artificial compounds, together with satisfying the strategy of 3Rs for laboratory use of animals. Our results indicated that all FUs display anti-oxidant and anti-steatotic activities. Steatotic FaO cells may be employed to further study the biological effects of FUs

Knocking down metabotropic glutamate receptor 1 improves survival and disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease reflecting degeneration of upper and lower motoneurons (MNs). The cause of ALS and the mechanisms of neuronal death are still largely obscure, thus impairing the establishment of efficacious therapies. Glutamate (Glu)-mediated excitotoxicity plays a major role in MN degeneration in ALS. We recently demonstrated that the activation of Group I metabotropic Glu autoreceptors, belonging to both type 1 and type 5 receptors (mGluR1 and mGluR5), at glutamatergic spinal cord nerve terminals, produces excessive Glu release in mice over-expressing human superoxide-dismutase carrying the G93A point mutation (SOD1G93A), a widely used animal model of human ALS. To establish whether these receptors are implicated in ALS, we generated mice expressing half dosage of mGluR1 in the SOD1G93A background (SOD1G93AGrm1crv4/+), by crossing the SOD1G93A mutant mouse with the Grm1crv4/+ mouse, lacking mGluR1 because of a spontaneous recessive mutation. SOD1G93AGrm1crv4/+ mice showed prolonged survival probability, delayed pathology onset, slower disease progression and improved motor performances compared to SOD1G93A mice. These effects were associated to reduction of mGluR5 expression, enhanced number of MNs, decreased astrocyte and microglia activation, normalization of metallothionein and catalase mRNA expression, reduced mitochondrial damage, and decrease of abnormal Glu release in spinal cord of SOD1G93AGrm1crv4/+compared to SOD1G93A mice. These results demonstrate that a lower constitutive level of mGluR1 has a significant positive impact on mice with experimental ALS, thus providing the rationale for future pharmacological approaches to ALS by selectively blocking Group I metabotropic Glu receptors

Percepção de Profissionais e Usuários de Unidades Básicas de Saúde sobre a Inserção do Nutricionista

Este estudo teve como objetivo analisar a importância da inserção do nutricionista em Unidades Básicas de Saúde (UBS), bem como as dificuldades de acesso aos seus serviços a partir da percepção de profissionais e usuários do serviço de saúde. Foi realizado um estudo de corte transversal de abordagem quantitativa e qualitativa, para o qual foram entrevistados profissionais e usuários de duas unidades básicas de saúde de Aracaju-SE utilizando-se um roteiro semiestruturado específico pré-testado e com gravação de áudio.  Para a análise das informações foi utilizada a técnica do Discurso do Sujeito Coletivo (DSC) proposta por Lefèvre e Lefèvre. Os resultados obtidos demonstraram que os profissionais e usuários têm conhecimento da importância do nutricionista nas UBS para melhoria da qualidade de vida da comunidade bem como para as trocas de informações e agregação de seu conhecimento aos demais profissionais da unidade, porém os mesmos relataram dificuldades para a ampliação e acesso a esse serviço, tais como: recursos humanos insuficientes, demora e burocracia no agendamento, e a falta de divulgação da presença do nutricionista nas unidades. Concluímos que, embora com sua importância reconhecida, a inserção do nutricionista na UBS esbarra em dificuldades relacionadas à burocracia, a falta de informação e aspectos relacionados à gestão.  Este estudio tuvo como objetivo analizar la importancia de la inserción de un nutricionista en las Unidades Básicas de Salud (UBS), así como las dificultades para acceder a sus servicios desde la percepción de los profesionales y usuarios del servicio de salud. Se realizó un estudio transversal con abordaje cuantitativo y cualitativo, para el cual se entrevistó a profesionales y usuarios de dos unidades básicas de salud en Aracaju-SE mediante un guión específico semiestructurado preprobado con grabación de audio. Para el análisis de la información se utilizó la técnica del Discurso Colectivo del Sujeto (DSC) propuesta por Lefèvre y Lefèvre. Los resultados obtenidos demostraron que los profesionales y usuarios son conscientes de la importancia del nutricionista en la UBS para mejorar la calidad de vida de la comunidad así como para el intercambio de información y la agregación de sus conocimientos al resto de profesionales de la unidad. sin embargo, informaron dificultades para la expansión y acceso a este servicio, tales como: insuficiencia de recursos humanos, demora y burocracia en la programación, y la falta de divulgación de la presencia de la nutricionista en las unidades. Concluimos que, a pesar de su reconocida importancia, la inserción del nutricionista en la UBS tropieza con dificultades relacionadas con la burocracia, la falta de información y aspectos relacionados con la gestión.This study aimed to analyze the importance of inserting a nutritionist in Basic Health Units (UBS), as well as the difficulties of accessing their services from the perception of professionals and users of the health service. A cross-sectional study with a quantitative and qualitative approach was carried out, for which professionals and users of two basic health units in Aracaju-SE were interviewed using a specific pre-tested script with audio recording. For the analysis of the information, the Collective Subject Discourse (DSC) technique proposed by Lefèvre and Lefèvre was used. The results obtained demonstrated that the professionals and users are aware of the importance of the nutritionist in the UBS for improving the quality of life of the community as well as for the exchange of information and the aggregation of their knowledge to the other professionals of the unit, however they reported difficulties for the expansion and access to this service, such as: insufficient human resources, delay and bureaucracy in scheduling, and the lack of disclosure of the presence of the nutritionist in the units. We conclude that, despite its recognized importance, the insertion of the nutritionist in the UBS comes up against difficulties related to bureaucracy, the lack of information and aspects related to management.Cette étude visait à analyser l'importance de l'insertion d'un nutritionniste dans les unités de santé de base (UBS), ainsi que les difficultés d'accès à leurs services du point de vue des professionnels et des utilisateurs du service de santé. Une étude transversale avec une approche quantitative et qualitative a été réalisée, pour laquelle des professionnels et des utilisateurs de deux unités de santé de base à Aracaju-SE ont été interrogés à l'aide d'un script semi-structuré spécifique pré-testé avec enregistrement audio. Pour l'analyse des informations, la technique du Discours Collectif Sujet (DSC) proposée par Lefèvre et Lefèvre a été utilisée. Les résultats obtenus ont démontré que les professionnels et utilisateurs sont conscients de l'importance du nutritionniste dans l'UBS pour améliorer la qualité de vie de la communauté ainsi que pour l'échange d'informations et l'agrégation de leurs connaissances avec les autres professionnels de l'unité. , cependant, ils ont signalé des difficultés pour l'expansion et l'accès à ce service, telles que: l'insuffisance des ressources humaines, les retards et la bureaucratie dans la planification, et le manque de divulgation de la présence du nutritionniste dans les unités. Nous concluons que, malgré son importance reconnue, l'insertion de la nutritionniste dans l'UBS se heurte à des difficultés liées à la bureaucratie, au manque d'information et aux aspects liés à la gestion

Fegato profumato. Gli aromi mediterranei lo proteggono dalla steatosi

Origano, maggiorana, santoreggia, timo, mentuccia, salvia e altre spezie aromatiche, tipiche della cucina mediterranea, non solo sono capaci di trasformare in un piatto eccellente pietanze semplici, ma attivano anche meccanismi biochimici che migliorano drasticamente il metabolismo lipidico, proteggendo il fegato dall\u2019accumulo di grassi

models of non alcoholic fatty liver disease and potential translational value the effects of 3 5 l diiodothyronine

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in industrialized countries and is associated with increased risk of cardiovascular, hepatic and metabolic diseases. Molecular mechanisms on the root of the disrupted lipid homeostasis in NAFLD and potential therapeutic strategies can benefit of in vivo and in vitro experimental models of fatty liver. Here, we describe the high fat diet (HFD)-fed rat in vivo model, and two in vitro models, the primary cultured rat fatty hepatocytes or the FaO rat hepatoma fatty cells, mimicking human NAFLD. Liver steatosis was invariably associated with increased number/size of lipid droplets (LDs) and modulation of expression of genes coding for key genes of lipid metabolism such as peroxisome proliferator-activated receptors (Ppars) and perilipins (Plins). In these models, we tested the anti-steatotic effects of 3,5-L-diiodothyronine (T2), a metabolite of thyroid hormones. T2 markedly reduced triglyceride content and LD size acting on mRNA expression of both Ppars and Plins. T2 also stimulated mitochondrial oxidative metabolism of fatty acids. We conclude that in vivo and especially in vitro models of NAFLD are valuable tools to screen a large number of compounds counteracting the deleterious effect of liver steatosis. Because of the high and negative impact of liver steatosis on human health, ongoing experimental studies from our group are unravelling the ultimate translational value of such cellular models of NAFLD