El estudio describe un mecanismo novedoso involucrado en la progresión de la enfermedad del hígado graso no alcohólico y destaca que la proteína Mitofusina 2 tiene el potencial de ser un posible modelo de tratamiento.
No alcohólico hígado graso la enfermedad es la más común hígado condition which affects people who drink no or very little alcohol. It affects 25 percent of global population and is quite prevalent in developed countries. The condition is characterized with accumulation of extra fat in hepatic cells leading to different liver dysfunctions. This condition is difficult to diagnose at an early stage. No treatment is available for non-alcoholic fatty hígado enfermedades y los médicos generalmente recomiendan perder peso. En una forma grave de esta enfermedad llamada esteatohepatitis no alcohólica (EHNA), la acumulación de grasa se acompaña de inflamación, muerte celular y fibrosis.
Un estudio publicado en Celular el 2 de mayo de 2019 propone una nueva posible diana terapéutica para el tratamiento de las grasas no alcohólicas enfermedad hepática. Researchers have identified a mitochondrial protein called Mitofusin 2 which could be one of the factors that can provide protection against this condition. In their study they saw that levels of Mitofusin 2 protein were seen to be low in patients suffering from NASH as seen from their hígado biopsies. The lower levels were present even in the early stages of NASH indicating that this disease develops when Mitofusin 2 protein decreases in the liver cells. A similar scenario was seen in hepatic cells of a mouse model of hígado graso no alcohólico disease .In mice the decrease in levels of Mitofusin 2 was responsible for hepatic inflammation, abnormal lipid metabolism, hígado fibrosis and liver cancer.
En experimentos llevados a cabo en un modelo de ratón de NASH, los ratones se colocaron bajo una dieta de pienso durante 2 semanas y se inyectaron por vía intravenosa en ratones adenovirus que codifican la proteína Mitofusina 2. El virus se modificó específicamente para expresar artificialmente las proteínas. Los hígados de estos ratones se analizaron después de 1 semana. Los resultados mostraron que se observó que la condición de NASH mejoraba en ratones con una mejora significativa en el metabolismo de los lípidos.
Detailed experiments revealed that membrane protein Mitofusin 2 directly binds to and aids transfer of phosphatidylserine (PS) which is primarily synthesised in the endoplasmic reticulum (ER). Mitofusin 2 extracts PS into membranes allowing transfer of PS to mitochondria where PS is converted to phosphatidylethanolamine (PE) to be sent to ER for making phosphatidylcholine. A deficiency in Mitofusin 2 causes reduction in transfer of PS from ER to mitochondria impairing lipid metabolism. This defective transfer leads to ER stress and causes NASH-like symptoms and cancer. It was clear that hepatic Mitofusin 2 gets downregulated in human liver during progression from simple steatosis to NASH. The study describes a novel function of Mitofusin 2 in maintenance of phospholipid metabolism. The link between Mitofusin 2 and phospholipids is particularly important because this can influence antioxidant, anti-inflammatory, anti-fibrotic properties and several membrane dependent functions. Re-expression of Mitofusin 2 in mice on chow diet improved the hígado enfermedad.
The current study describes a novel previously unreported mechanism for development of non-alcoholic fatty liver disease and highlights Mitofusin 2 protein as a possible new therapeutic target for treating non-alcoholic fatty hígado disease. Future studies shall focus on various approaches which could enhance the levels of Mitofusin 2 without causing side effects.
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{Puede leer el trabajo de investigación original haciendo clic en el enlace DOI que figura a continuación en la lista de fuentes citadas}
Fuentes)
Hernández-Alvarez MI. et al. 2019. La transferencia deficiente del retículo endoplásmico-fosfatidilserina mitocondrial causa enfermedad hepática. Celda, 177 (4). https://doi.org/10.1016/j.cell.2019.04.010
