Do Intestinal Unicellular Parasites Have a Role in the Inflammatory and Redox Status among the Severely Obese?

The diagnosis of obesity comprises subjects with totally different phenotypes and metabolic profiles. Systemic inflammation and oxidative stress derived from the white adipose tissue are suggested as the link between this disease and the development of insulin resistance and metabolic comorbidities. The presence of unicellular eukaryotic parasites colonizing the human gut ecosystem is a common circumstance, and yet their influence on the inflammatory and redox status of the obese host has not been assessed. Herein, a set of inflammatory and redox biomarkers were assessed together with a parasitological analysis of 97 severely obese subjects. Information was also collected on insulin resistance and on the antioxidant composition of the diet. The global prevalence of intestinal unicellular parasites was 49.5%, with Blastocystis sp. the most prevalent protozoan found (42.3%). Colonized subjects displayed a higher total antioxidant capacity and a trend towards higher extracellular superoxide dismutase activity, regardless of their insulin resistance status, along with lower reduced glutathione/oxidized glutathione (GSH/GSSG) ratios in plasma in the insulin-resistant subgroup. No changes in malondialdehyde levels, or in inflammatory cytokines in plasma, were found in regard to the colonization status. In conclusion, enteric eukaryotic unicellular parasites may play an important role in modulating the antioxidant defenses of an obese host, thus could have beneficial effects with respect to the development of systemic metabolic disorders.

Role of adenosine receptors in the adipocyte-macrophage interaction during obesity. / Rol de los receptores de adenosina en la interacción adipocito-macrófago durante la obesidad.

Lipoinflamation is the inflammation generated in the adipose tissue. It can contribute to the development of insulin resistance. The lipoinflammation-associated mechanisms are related to the function of adipocytes and macrophages present in the adipose tissue. In this regard, the level of nucleoside adenosine is increased in individuals with obesity. Causes or consequences of this increase are unknown. Although, adenosine activating its receptors (A1, A2A, A2B and A3) is able to differentially modulate the function of adipocytes and macrophages, in order to avoid the reduction of insulin sensitivity and generate an anti-inflammatory state in subject with obesity. In this review we propose that adenosine could be a key element in the development of new strategies for limit lipoinflammation and regulate metabolic homeostasis through modulation of adipocyte-macrophage dialogue.

Mecanismos implicados en la aparición y regulación del proceso de remodelación del tejido adiposo y estado de lipoinflamación en la obesidad / Mechanisms involved in occurence and regulation of the process of adipose tissue remodelation and the state of lipoinflammation in obesity

INTRODUCCIÓN: la obesidad se acompaña de un estado inflamatorio crónico, lo cual trae efectos negativos a la salud. OBJETIVO: describir los mecanismos implicados en la aparición y regulación del proceso de remodelación del tejido adiposo y estado de lipoinflamación en la obesidad. MÉTODOS: se realizó una búsqueda en Medline/PubMed y Bireme, de artículos publicados en inglés y español en el período comprendido entre enero de 2006 y diciembre de 2015. Los términos de búsqueda fueron energy balance, regulation, nutritional homeostasis. DESARROLLO: las alteraciones del balance energético positivo determinan un balance de energía incrementado en el adipocito, en el cual ocurre hiperplasia e hipertrofia, lo que provoca resistencia molecular, hiperproducción de ácidos grasos libres, adipocitocinas y mediadores inflamatorios con promoción de disfunción sistémica; al mismo tiempo que se produce una hipoxia. Esta hipoxia provoca cambios en la expresión de algunas adipocinas y citocinas inflamatorias, y la muerte celular de los adipocitos más periféricos, que se traduce en un aumento de la reacción inflamatoria, la cual aumenta con la transformación de los macrófagos secretores de adipocitocinas antiinflamatorias a macrófagos secretores de adipocitocinas proinflamatorias, e infiltración de estos últimos en el tejido adiposo, todo lo cual lleva a una disregulación de la homeostasis. CONSIDERACIONES FINALES: existen diferentes mecanismos implicados en la aparición y regulación del proceso de remodelación del tejido adiposo y estado de lipoinflamación en la obesidad, los cuales determinan una comunicación alterada del tejido adiposo con otros órganos.

INTRODUCTION: obesity is accompanied by chronic inflammatory condition and brings negative health effects. OBJECTIVE: to describe the mechanisms involved in occurence and regulation of the process of adipose tissue remodelling and state of lipoinflammation in obesity. METHODS: a search of articles published in English and Spanish from January 2006 to December 2015 was made in Medline/PubMed and Bireme. The search terms were energy balance, regulation, and nutritional homeostasis. DEVELOPMENT: alterations in the positive energy balance determine an increased energy balance in the adipocyte in which hiperplasia and hypertrophy occur, which leads to molecular resistance, hyperproduction of free fatty acids, adipocytokines and inflammatory mediators with promotion of systemic dysfunction and at the same time hipoxia. Hypoxia causes changes in expression of some inflammatory adipokines and cytokines and the cell death of most peripheral adipocytes, all of which leads to increase of inflammatory reactions, the transformation of anti-inflammatory adipocytokine secretion macrophages into proinflammatory adipocytokine secretion macrophages and the infiltration of the latter in the adipose tissue and finally to homeostasis deregulation. FINAL THOUGHTS: there are several mechanisms involved in occurence and regulation of the process of the adipose tissue remodelling and state of lipoinflammation in obesity and they determine an altered communication of the adipose tissue with other body organs.

Mecanismos implicados en la aparición y regulación del proceso de remodelación del tejido adiposo y estado de lipoinflamación en la obesidad / Mechanisms involved in occurence and regulation of the process of adipose tissue remodelation and the state of lipoinflammation in obesity

Introducción: la obesidad se acompaña de un estado inflamatorio crónico, lo cual trae efectos negativos a la salud.Objetivo: describir los mecanismos implicados en la aparición y regulación del proceso de remodelación del tejido adiposo y estado de lipoinflamación en la obesidad.Métodos: se realizó una búsqueda en Medline/PubMed y Bireme, de artículos publicados en inglés y español en el período comprendido entre enero de 2006 y diciembre de 2015. Los términos de búsqueda fueron energy balance, regulation, nutritional homeostasis.Desarrollo: las alteraciones del balance energético positivo determinan un balance de energía incrementado en el adipocito, en el cual ocurre hiperplasia e hipertrofia, lo que provoca resistencia molecular, hiperproducción de ácidos grasos libres, adipocitocinas y mediadores inflamatorios con promoción de disfunción sistémica; al mismo tiempo que se produce una hipoxia. Esta hipoxia provoca cambios en la expresión de algunas adipocinas y citocinas inflamatorias, y la muerte celular de los adipocitos más periféricos, que se traduce en un aumento de la reacción inflamatoria, la cual aumenta con la transformación de los macrófagos secretores de adipocitocinas antiinflamatorias a macrófagos secretores de adipocitocinas proinflamatorias, e infiltración de estos últimos en el tejido adiposo, todo lo cual lleva a una disregulación de la homeostasis.Consideraciones finales: existen diferentes mecanismos implicados en la aparición y regulación del proceso de remodelación del tejido adiposo y estado de lipoinflamación en la obesidad, los cuales determinan una comunicación alterada del tejido adiposo con otros órganos(AU)

Hepatocytes release ceramide-enriched pro-inflammatory extracellular vesicles in an IRE1α-dependent manner.

Nonalcoholic steatohepatitis (NASH) is a lipotoxic disease wherein activation of endoplasmic reticulum (ER) stress response and macrophage-mediated hepatic inflammation are key pathogenic features. However, the lipid mediators linking these two observations remain elusive. We postulated that ER stress-regulated release of pro-inflammatory extracellular vesicles (EVs) from lipotoxic hepatocytes may be this link. EVs were isolated from cell culture supernatants of hepatocytes treated with palmitate (PA) to induce lipotoxic ER stress, characterized by immunofluorescence, Western blotting, electron microscopy, and nanoparticle tracking analysis. Sphingolipids were measured by tandem mass spectrometry. EVs were employed in macrophage chemotaxis assays. PA induced significant EV release. Because PA activates ER stress, we used KO hepatocytes to demonstrate that PA-induced EV release was mediated by inositol requiring enzyme 1α (IRE1α)/X-box binding protein-1. PA-induced EVs were enriched in C16:0 ceramide in an IRE1α-dependent manner, and activated macrophage chemotaxis via formation of sphingosine-1-phosphate (S1P) from C16:0 ceramide. This chemotaxis was blocked by sphingosine kinase inhibitors and S1P receptor inhibitors. Lastly, elevated circulating EVs in experimental and human NASH demonstrated increased C16:0 ceramide. PA induces C16:0 ceramide-enriched EV release in an IRE1α-dependent manner. The ceramide metabolite, S1P, activates macrophage chemotaxis, a potential mechanism for the recruitment of macrophages to the liver under lipotoxic conditions.