[Molecular basis of obesity-related hepatic steatosis]. / Fundamento molecular de la esteatosis hepática asociada a la obesidad.

Non-alcoholic fatty liver disease is a chronic inflammation liver condition that is currently highly relevant because of its strong association with increasingly incident diseases such as obesity and type-2 diabetes mellitus. The primary purpose of this paper is to discuss the best part of current knowledge on the molecular mechanisms involved in hepatic steatosis development, the condition s initial stage, and on progression to steatohepatitis. Special attention has been paid to clinical and experimental obesity-related fatty liver. In the latter, the fa/fa rat is assessed, which constitutes an animal model for obesity with phenotype features similar to human obesity, including insulin resistance and dyslipemia. Hepatic steatosis is a complex, mainly metabolic condition where apparently non-compatible metabolic processes concur, in addition to oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and decreased expression of survival genes. Extrahepatic signals underlie the disorder, such as those arising from peripheral insulin resistance associated with an increase in adipose mass and systemic free fatty acids, together with intrahepatic signals leading to derangement of liver glycostatic and lipidostatic functions, as well as to greater vulnerability to other aggressions.

Fundamento molecular de la esteatosis hepática asociada a la obesidad / No disponible

La enfermedad del hígado graso no alcohólico es una enfermedadinflamatoria hepática de carácter crónico de gran relevanciaen la actualidad por su fuerte asociación con enfermedades de incidenciacreciente como la obesidad y la diabetes mellitus tipo 2.En este trabajo se recoge buena parte del conocimiento existentesobre los mecanismos moleculares implicados en el establecimientode la esteatosis hepática, el primer estadio de la enfermedad, yen su progreso a esteatohepatitis. Se ha prestado una atención especialal hígado graso asociado a la obesidad, clínica y experimental.En este caso, se valora la rata fa/fa, un modelo animal de obesidadcon rasgos fenotípicos similares a los de la obesidadhumana, incluyendo la resistencia a la insulina y la dislipemia. Laesteatosis hepática se revela como una situación compleja, eminentementemetabólica, en la que se simultanean procesos metabólicosaparentemente contradictorios, así como estrés oxidativo,estrés de retículo endoplasmático, disfunción mitocondrial y descensoen la expresión de genes de supervivencia. En buena medida,en su base se sitúan señales extrahepáticas, como las producidasen una situación de resistencia periférica a la insulina asociadaa un aumento de la masa adiposa y de ácidos grasos libres sistémicos,e internas, causantes de un desajuste de las funciones glucostáticay lipidostática del hígado y de una mayor vulnerabilidad aotras agresiones

Non-alcoholic fatty liver disease is a chronic inflammation livercondition that is currently highly relevant because of its strong associationwith increasingly incident diseases such as obesity andtype-2 diabetes mellitus. The primary purpose of this paper is todiscuss the best part of current knowledge on the molecular mechanismsinvolved in hepatic steatosis development, the condition’sinitial stage, and on progression to steatohepatitis. Special attentionhas been paid to clinical and experimental obesity-related fattyliver. In the latter, the fa/fa rat is assessed, which constitutes ananimal model for obesity with phenotype features similar to humanobesity, including insulin resistance and dyslipemia. Hepaticsteatosis is a complex, mainly metabolic condition where apparentlynon-compatible metabolic processes concur, in addition tooxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction,and decreased expression of survival genes. Extrahepaticsignals underlie the disorder, such as those arising from peripheralinsulin resistance associated with an increase in adipose mass andsystemic free fatty acids, together with intrahepatic signals leadingto derangement of liver glycostatic and lipidostatic functions, aswell as to greater vulnerability to other aggressions