Utafiti unafafanua utaratibu wa riwaya unaohusika katika maendeleo ya ugonjwa wa ini usio na ulevi na inaangazia protini Mitofusin 2 kuwa na uwezo wa kuwa mfano wa matibabu unaowezekana.
Mashirika yasiyo ya pombe ini ya mafuta ugonjwa ndio unaojulikana zaidi ini 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 ini ugonjwa na madaktari kwa ujumla hupendekeza kupoteza uzito. Katika aina mbaya ya ugonjwa huu uitwao non-alcoholic steatohepatitis (NASH), mkusanyiko wa mafuta unaambatana na kuvimba, kifo cha seli na fibrosis.
Utafiti uliochapishwa katika Kiini tarehe 2 Mei 2019 inapendekeza lengo jipya linalowezekana la matibabu kwa ajili ya kutibu mafuta yasiyo ya kileo ugonjwa wa ini. 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 ini 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 ini ya mafuta yasiyo ya pombe disease .In mice the decrease in levels of Mitofusin 2 was responsible for hepatic inflammation, abnormal lipid metabolism, ini fibrosis and liver cancer.
Katika majaribio yaliyofanywa kwenye modeli ya panya ya NASH, panya waliwekwa chini ya lishe ya chow kwa wiki 2 na adenoviruses zinazosimba protini ya Mitofusin 2 zilidungwa ndani ya panya kwa njia ya mshipa. Virusi vilirekebishwa mahsusi ili kuelezea protini kisanii. Ini za panya hawa zilichambuliwa baada ya wiki 1. Matokeo yalionyesha kuwa hali ya NASH ilionekana kuboreka kwa panya na uboreshaji mkubwa katika kimetaboliki ya lipid.
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 ini ugonjwa huo.
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 ini disease. Future studies shall focus on various approaches which could enhance the levels of Mitofusin 2 without causing side effects.
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Chanzo (s)
Hernández-Alvarez MI. na wengine. 2019. Upungufu wa Uhamisho wa Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Husababisha Ugonjwa wa Ini. Kiini, 177 (4). https://doi.org/10.1016/j.cell.2019.04.010
