Pētījumā aprakstīts jauns mehānisms, kas saistīts ar bezalkoholisko taukainu aknu slimību progresēšanu, un uzsvērts, ka proteīns Mitofusīns 2 var būt iespējams ārstēšanas modelis.
Bezalkoholisks treknas aknas slimība ir visizplatītākā aknas 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 aknas slimība un ārsti parasti iesaka zaudēt svaru. Šīs slimības smagā formā, ko sauc par bezalkoholisko steatohepatītu (NASH), tauku uzkrāšanos pavada iekaisums, šūnu nāve un fibroze.
Pētījums publicēts Šūna 2. gada 2019. maijā piedāvā jaunu iespējamo terapeitisko mērķi bezalkoholisko tauku ārstēšanai aknu slimība. 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 aknas 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 bezalkoholiskas taukainas aknas disease .In mice the decrease in levels of Mitofusin 2 was responsible for hepatic inflammation, abnormal lipid metabolism, aknas fibrosis and liver cancer.
Eksperimentos, kas tika veikti ar NASH peles modeli, pelēm uz 2 nedēļām tika piemērota čau diēta, un pelēm intravenozi injicēja adenovīrusus, kas kodē Mitofusin 2 proteīnu. Vīruss tika īpaši pārveidots, lai mākslīgi ekspresētu olbaltumvielas. Šo peļu aknas tika analizētas pēc 1 nedēļas. Rezultāti parādīja, ka NASH stāvoklis pelēm uzlabojās, ievērojami uzlabojoties lipīdu metabolismam.
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 aknas slimība.
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 aknas disease. Future studies shall focus on various approaches which could enhance the levels of Mitofusin 2 without causing side effects.
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Avots (-i)
Hernandess-Alvaress, MI. un citi. 2019. Deficīts endoplazmatiskā retikula-mitohondriju fosfatidilserīna pārnešana izraisa aknu slimību. Cell, 177 (4). https://doi.org/10.1016/j.cell.2019.04.010
