The influence of endotoxemia on the molecular mechanisms of insulin resistance La influencia de la endotoxemia en los mecanismos moleculares de resistencia a la insulina

Introduction: The reduction in the capacity of insulin to reach its biological effects can lead to a chronic hyperglycemia and hyperinsulinemia, assuming an important role in the pathogenesis of metabolic disorders associated to obesity and diabetes. Insulin resistance is associated to chronic subclinical inflammation, which in part can be mediated by increased plasmatic lipopolysaccharide levels, an endotoxin derived from the membrane of gramnegative bacteria that mainly reside in the gut. Objectives: The aim of this review study is to describe the molecular mechanisms involved in the pathogenesis of insulin resistance due to metabolic endotoxemia and of its connection to obesity and diabetes. Results and discussion: Lipopolysaccharide present in the intestinal lumen can reach the circulatory system causing metabolic endotoxemia. When lipopolysaccharide binds to Toll-like receptor 4, inflammation is activated, changing several stages of insulin signaling. It has been shown that chronic exposure to this endotoxin may contribute to weight gain and type 2 diabetes mellitus manifestation. Obese and diabetic people have increased plasmatic lipopolysaccharide levels. The increase in the number of gram-negative bacteria on gut microbiota, the reduction on gut mucosal integrity, and the consumption of high-fat diets increase the plasmatic lipopolysaccharide levels. Therefore, the type of diet consumed may modulate the composition of gut microbiota and improve gut mucosal integrity, decreasing the occurrence of endotoxemia and its postprandial inflammatory effects, leading to adequate insulin signaling. However, there are very few studies that evaluated the influence of nutrients and/or specific food types on metabolic endotoxemia.Introducción: La reducción de la capacidad de de la insulina para alcanzar sus efectos biológicos puede inducir a un proceso crónico de la hiperglucemia y la hiperinsulinemia, asumiendo un rol de importancia en la patogénesis de las alteraciones metabólicas relacionadas con la obesidad y la diabetes. Esta resistencia a la insulina se conecta a la inflamación crónica subclínica que, en parte, podría estar mediado por el aumento de los niveles plasmáticos de lipopolisacárido, una endotoxina derivada de la membrana de las bactérias gram-negativas que reside principalmente en el intestino. Objetivos: El objetivo de esta revisión es describir los mecanismos moleculares implicados en la patogénesis de la resistencia a la insulina que surgen a