Modelos animales experimentales de enfermedad de hígado graso y síndrome metabólico / Experimental animal models of fatty liver disease and metabolic syndrome

Los estudios en modelos animales constituyen una valiosa herramienta para comprender los procesos fisiopatológicos asociados a la enfermedad del hígado graso, sus características histológicas y ensayo de nuevas terapias. Una gran parte de los trabajos se desarrollan en roedores (ratones y ratas principalmente), dada su similitud biológica con el hombre y el gran conocimiento que se tiene a todos los niveles (genético, molecular, enzimático…) de estas especies. Por su facilidad de desarrollar los procesos de esteatosis hepática también destacan las aves. En este trabajo se describen los principales modelos de enfermedad del hígado graso en diversas especies animales, y las formas de inducción de enfermedad. Básicamente, el excesivo acúmulo de grasa en hígado puede ser consecuencia de aporte elevado de grasa, aumento de la síntesis grasa, oxidación reducida, y/o reducción de su salida en forma de VLDL. Así, se describen modelos basados en alteraciones genéticas (animales transgénicos o bien mutaciones naturales) que incrementan la lipogénesis, otros que dificultan la eliminación de grasa hepática (genes que regulan la oxidación de ácidos grasos), inducción mediante dietas que dan lugar a obesidad (ricas en fructosa, sacarosa, grasas, dietas aterogénicas) o bien sin producir obesidad (dietas deficientes en arginina o ricas en fructosa y grasas), tóxicos que incrementan la lipogénesis hepática, o factores que disminuyen la oxidación de ácidos grasos (como dietas deficientes en colina o metionina, administración de estrógenos, glucocorticoides o ciertos tóxicos). Se describen por último modelos aviares inducidos por la dieta (AU)

Animal models are important tools for the study of fatty liver disease, mainly related to physiopathology, pathology and therapeutical trials. Most studies have been developed in rodents (usually in mice and rats), because of biological similarities with humans, and also because of the deep knowledge (genetics, molecular, enzymatic…) of these species. Hepatic steatosis is also easily developed in avian species. We describe the most used animal models of fatty liver disease, and the several means of disease induction. Basically, excessive fat accumulation in the liver can occur as a result of increased fat delivery, increased fat synthesis, reduced fat oxidation, and/or reduced fat export in the form of VLDL. Several animal models of hepatic steatosis are described: genetically engineered animals or spontaneous mutations, which increase lipogenesis; others show reduced fatty acid oxidation, and therefore interfere fat elimination; induction by diets producing obesity: high content in fructose, sacarose, fat, and atherogenic diets; induction by diets which don’t produce obesity (arginine deficient diets), toxic agents which increase hepatic lipogenesis, or factors inducing a decrease of fatty acid oxidation such as choline / methionine deficient diets, strogens and glucocorticoids administration, or toxic agents. Diet-induced avian models are also described (AU)

Perfusion of trout liver in situ. Description and validation of the technique.

The aim of this study was to develop a method for perfusing isolated trout livers that would make it possible to study hepatic metabolism in the whole organ. Rainbow trout (Oncorhynchus mykiss Walbaum) subjected to different fasting periods of 24, 48 or 96 h were used in all the experiments. A non-recirculating system was applied at a flow rate of 0.2 mL/min. The perfusion medium was a specific saline solution for salmonids oxygenated by a multi-bulb glass oxygenator. Viability assays included the measurement of oxygen consumption, lactate dehydrogenase activity and liver metabolic capacity. In addition, a histological study was carried out. Our results showed that the metabolic capacity of the liver survived throughout the perfusion process and that the functioning of this organ changed depending on the length of the fasting period to which the animal had been submitted. The method described here was shown to be suitable for studying the intermediate metabolism of fish.