Rannsókn lýsir nýjum aðferðum sem taka þátt í framgangi óáfengs fitulifrarsjúkdóms og undirstrikar prótein Mítófúsín 2 sem hugsanlegt meðferðarlíkan
Non-alkóhólisti feitur lifur sjúkdómur er algengastur lifur 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 lifur Sjúkdómurinn og læknar mæla almennt með að léttast. Í alvarlegri mynd þessa sjúkdóms sem kallast óalkóhólísk fituhepatibólga (NASH), fylgir fitusöfnun bólgu, frumudauði og bandvefssjúkdómur.
Rannsókn sem birt var í Cell maí 2 leggur til nýtt hugsanlegt meðferðarmarkmið til að meðhöndla óáfenga fitu. lifrarsjúkdóm. 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 lifur 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 óáfenga fitulifur disease .In mice the decrease in levels of Mitofusin 2 was responsible for hepatic inflammation, abnormal lipid metabolism, lifur fibrosis and liver cancer.
Í tilraunum sem gerðar voru á músarlíkani af NASH voru mýs settar undir matarfæði í 2 vikur og adenoveirur sem kóða Mítófúsín 2 prótein voru sprautaðar í mýs í bláæð. Veiran var sérstaklega breytt til að tjá próteinin með tilbúnum hætti. Lifur þessara músa voru greind eftir 1 viku. Niðurstöður sýndu að ástand NASH batnaði hjá músum með marktækum framförum á fituefnaskiptum.
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 lifur sjúkdómur.
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 lifur disease. Future studies shall focus on various approaches which could enhance the levels of Mitofusin 2 without causing side effects.
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{Þú getur lesið upprunalegu rannsóknarritgerðina með því að smella á DOI hlekkinn sem gefinn er upp hér að neðan á listanum yfir tilvitnaðar heimildir}
Heimildir)
Hernández-Alvarez MI. o.fl. 2019. Skortur endoplasmic reticulum-mitochondrial fosfatidýlserínflutningur veldur lifrarsjúkdómum. Cell, 177 (4). https://doi.org/10.1016/j.cell.2019.04.010
