ABSTRACT
Extracellular vesicles (EVs) are well-known mediators in intercellular communication playing pivotal roles in promoting liver inflammation and fibrosis, events associated to hepatic lipotoxicity caused by saturated free fatty acid overloading. However, despite the importance of lipids in EV membrane architecture which, in turn, affects EV biophysical and biological properties, little is known about the lipid asset of EVs released under these conditions. Here, we analyzed phospholipid profile alterations of EVs released by hepatocarcinoma Huh-7 cells under increased membrane lipid saturation induced by supplementation with saturated fatty acid palmitate or Δ9 desaturase inhibition, using oleate, a nontoxic monounsaturated fatty acid, as control. As an increase of membrane lipid saturation induces endoplasmic reticulum (ER) stress, we also analyzed phospholipid rearrangements in EVs released by Huh-7 cells treated with thapsigargin, a conventional ER stress inducer. Results demonstrate that lipotoxic and/or ER stress conditions induced rearrangements not only into cell membrane phospholipids but also into the released EVs. Thus, cell membrane saturation level and/or ER stress are crucial to determine which lipids are discarded via EVs and EV lipid cargos might be useful to discriminate hepatic lipid overloading and ER stress.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Extracellular Vesicles/metabolism , Fatty Acids/adverse effects , Liver Neoplasms/metabolism , Membrane Lipids/metabolism , Cell Line, Tumor , Endoplasmic Reticulum Stress/drug effects , Extracellular Vesicles/drug effects , Humans , Oleic Acid/adverse effects , Palmitic Acid/adverse effectsABSTRACT
Anemia is a most common complication of inflammatory bowel disease. A high frequency of low hemoglobin values in these patients often leads physicians to subestimate this condition, which translates into ineffective treatment. On the other hand, the complex nature of anemia-inducing mechanisms in inflammatory bowel disease frequently raises doubt about the most appropriate therapy. A correct identification of patients with anemia, and adequate therapy are the essential pillars for improved quality of life. The right use of iron supplementation, and novel parenteral iron formulations, either with or without associated erythropoietin, have revolutionized our approach of this complication in the course of inflammatory bowel disease.
Subject(s)
Anemia, Iron-Deficiency/etiology , Inflammatory Bowel Diseases/complications , Decision Trees , HumansABSTRACT
La anemia es una de las complicaciones más comunes de la enfermedadinflamatoria intestinal. La alta frecuencia de valores bajosde hemoglobina en estos enfermos provoca en muchas ocasionesuna infravaloración por parte del médico de esta circunstancia, loque se traduce en la falta de un tratamiento eficaz. Por otro lado, elcarácter complejo de los mecanismos de producción de la anemiaen la enfermedad inflamatoria intestinal con frecuencia plantea dudasacerca del tratamiento más adecuado. La identificación correctade los pacientes con anemia así como la instauración del tratamientomás idóneo serán los dos pilares fundamentales para lamejoría de la calidad de vida de los enfermos. El uso correcto delos suplementos de hierro y las nuevas formulaciones de hierro parenteral,con o sin eritropoyetina asociada, han revolucionadonuestro abordaje de esta complicación evolutiva de la enfermedadinflamatoria intestinal
Anemia is a most common complication of inflammatory boweldisease. A high frequency of low hemoglobin values in thesepatients often leads physicians to subestimate this condition,which translates into ineffective treatment. On the other hand, thecomplex nature of anemia-inducing mechanisms in inflammatorybowel disease frequently raises doubt about the most appropriatetherapy. A correct identification of patients with anemia, and adequatetherapy are the essential pillars for improved quality of life.The right use of iron supplementation, and novel parenteral ironformulations, either with or without associated erythropoietin,have revolutionized our approach of this complication in thecourse of inflammatory bowel disease