{"id":11390,"date":"2018-10-15T13:17:06","date_gmt":"2018-10-15T12:17:06","guid":{"rendered":"http:\/\/www.cri1149.fr\/?p=11390"},"modified":"2025-12-03T18:02:35","modified_gmt":"2025-12-03T17:02:35","slug":"inhibition-of-monoacylglycerol-lipase-an-anti-inflammatory-and-antifibrogenic-strategy-in-the-liver","status":"publish","type":"post","link":"https:\/\/cri1149.fr\/en\/actualites\/inhibition-of-monoacylglycerol-lipase-an-anti-inflammatory-and-antifibrogenic-strategy-in-the-liver\/","title":{"rendered":"Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver."},"content":{"rendered":"<p style=\"text-align: center;\"><strong><a href=\"https:\/\/www-ncbi-nlm-nih-gov.gate2.inist.fr\/pubmed\/30301768\"><span style=\"color: #808080;\">Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver.<\/span><\/a><\/strong><\/p>\n<p style=\"text-align: justify;\">Habib A, Chokr D, Wan J, Hegde P, Mabire M, Siebert M, Ribeiro-Parenti L, Le Gall M, Lett\u00e9ron P, Pilard N, Mansouri A, Brouillet A, Tardelli M, Weiss E, Le Faouder P, Guillou H, Cravatt BF, Moreau R, Trauner M,\u00a0<strong>Lotersztajn<\/strong>\u00a0S.<\/p>\n<p style=\"text-align: justify;\">Gut. 2018 Oct 9. pii: gutjnl-2018-316137. doi: 10.1136\/gutjnl-2018-316137. [Epub ahead of print]<\/p>\n<p style=\"text-align: justify;\">PMID:\u00a030301768<\/p>\n<p style=\"text-align: center;\">\u00a0<a href=\"https:\/\/gut.bmj.com\/content\/early\/2018\/10\/09\/gutjnl-2018-316137.long\" target=\"_blank\" rel=\"noopener noreferrer\">https:\/\/gut.bmj.com\/content\/early\/2018\/10\/09\/gutjnl-2018-316137.long<\/a><\/p>\n<p style=\"text-align: justify;\">Significance of the study<\/p>\n<p style=\"text-align: justify;\"><strong>What is already known on this subject?<\/strong><\/p>\n<p style=\"text-align: justify;\">\u25ba\u25ba Cirrhosis lacks treatment, and liver transplantation is considered as the only option for end-stage liver disease, which justifies past and ongoing massive efforts to identify potential therapeutic antifibrotic targets.<\/p>\n<p style=\"text-align: justify;\">\u25ba\u25ba Sustained inflammation originating from resident and infiltrating immune cells drives the fibrogenic process during liver injury, and contributes to its resolution, and targeting<\/p>\n<p style=\"text-align: justify;\">macrophages is an attractive antifibrogenic strategy.<\/p>\n<p style=\"text-align: justify;\">\u25ba\u25ba Monoacylglycerol lipase (MAGL) is a proinflammatory enzyme that produces arachidonic acid from the endocannabinoid 2-arachidonoylglycerol and serves as a connecting metabolic hub between endocannabinoid and lipid signalling network.<\/p>\n<p style=\"text-align: justify;\"><strong>What are the new findings?<\/strong><\/p>\n<p style=\"text-align: justify;\">\u25ba\u25ba MAGL invalidation in myeloid cells is sufficient to reduce inflammation and fibrosis progression.<\/p>\n<p style=\"text-align: justify;\">\u25ba\u25ba Therapeutic intervention with MAGL inhibitors slows down fibrosis progression and reverses established fibrosis.<\/p>\n<p style=\"text-align: justify;\">\u25ba\u25ba In vivo and in vitro, anti-inflammatory and antifibrogenic effects of MAGL inhibitors are mediated by autophagy in macrophages.<\/p>\n<p style=\"text-align: justify;\"><strong>How might it impact on clinical practice in the foreseeable future?<\/strong><\/p>\n<p style=\"text-align: justify;\">\u25ba\u25ba MAGL inhibitors are promising antifibrogenic compounds that may prove useful during fibrosis progression and in the context of fibrosis regression.<\/p>\n<p style=\"text-align: justify;\">La fibrose et son stade ultime, la cirrhose sont la cons\u00e9quence de toutes les maladies chroniques du foie.\u00a0et reste un probl\u00e8me de sant\u00e9 publique pr\u00e9occupant, avec une pr\u00e9valence d\u2019environ 2 pour 1000 et 14000 d\u00e9c\u00e8s\/an. N\u00e9anmoins, il n\u2019existe \u00e0 ce jour aucune mol\u00e9cule dont l\u2019effet antifibrosant ait \u00e9t\u00e9 valid\u00e9 en pratique clinique.L\u2019inflammation exacerb\u00e9e est caract\u00e9ristique des maladies chroniques du foie et contribue \u00e0 leur progression vers des stades plus s\u00e9v\u00e8res.\u00a0Un traitement permettant une r\u00e9gulation de la r\u00e9ponse inflammatoire est aujourd\u2019hui consid\u00e9r\u00e9 comme une approche anti-fibrog\u00e9nique int\u00e9ressante.\u00a0Le macrophage est une cible de choix car son r\u00f4le dans la progression et la r\u00e9gr\u00e9ssion de la fibrose est bien \u00e9tabli.<\/p>\n<p style=\"text-align: justify;\">Au cours de ce travail, nous d\u00e9montrons que la reprogrammation du m\u00e9tabolisme lipidique du macrophage pourrait constituter une pproche anti-fibrosante int\u00e9ressante. Nous avons \u00e9tudi\u00e9 le r\u00f4le d&#8217;une enzyme, la monoacylglycerol lipase, responsable de la d\u00e9gradation de monoacylglycerols en acide arachidonique. En combinant des approches in vivo \u00e0 l\u2019aide de souris invalid\u00e9es s\u00e9lectivement pour cette enzyme dans le macrophage \u00e0 des approches pharmacologiques, nous d\u00e9montrons que des inhibiteurs de cet\u00a0enzyme diminuent l&#8217;inflammation h\u00e9patique en ciblant le macrophage, ralentissent la progression de la fibrose et acc\u00e9l\u00e8rent sa\u00a0r\u00e9gression.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>L&#8217;\u00e9quipe de Sophie Lotersztajn publie dans &#8220;Gut&#8221; 2018<\/p>\n","protected":false},"author":9,"featured_media":11392,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_EventAllDay":false,"_EventTimezone":"","_EventStartDate":"","_EventEndDate":"","_EventStartDateUTC":"","_EventEndDateUTC":"","_EventShowMap":false,"_EventShowMapLink":false,"_EventURL":"","_EventCost":"","_EventCostDescription":"","_EventCurrencySymbol":"","_EventCurrencyCode":"","_EventCurrencyPosition":"","_EventDateTimeSeparator":"","_EventTimeRangeSeparator":"","_EventOrganizerID":[],"_EventVenueID":[],"_OrganizerEmail":"","_OrganizerPhone":"","_OrganizerWebsite":"","_VenueAddress":"","_VenueCity":"","_VenueCountry":"","_VenueProvince":"","_VenueState":"","_VenueZip":"","_VenuePhone":"","_VenueURL":"","_VenueStateProvince":"","_VenueLat":"","_VenueLng":"","_VenueShowMap":false,"_VenueShowMapLink":false,"footnotes":""},"categories":[85],"tags":[],"class_list":["post-11390","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-actualites"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - 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