{"id":3331,"date":"2026-04-06T06:54:25","date_gmt":"2026-04-06T06:54:25","guid":{"rendered":"https:\/\/medicine.nus.edu.sg\/medphc\/?p=3331"},"modified":"2026-04-06T06:54:25","modified_gmt":"2026-04-06T06:54:25","slug":"targeted-inhibition-of-hepatic-de-novo-ceramide-synthesis-ameliorates-mash","status":"publish","type":"post","link":"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/targeted-inhibition-of-hepatic-de-novo-ceramide-synthesis-ameliorates-mash\/","title":{"rendered":"Targeted inhibition of hepatic de novo ceramide synthesis ameliorates MASH"},"content":{"rendered":"

\"\"<\/p>\n

Abstract<\/h2>\n

Increasing evidence implicates ceramides in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). However, the therapeutic potential of liver-targeted ceramide lowering remains unclear. In this study, we demonstrate that elevated ceramide levels in MASH patients and mouse models are closely associated with the activation of hepatic de novo ceramide synthesis. The analysis of human hepatic single-nucleus RNA sequencing (snRNA-seq) data revealed predominant up-regulation of SPTLC2<\/i>, which encodes a subunit of the rate-limiting enzyme in the de novo ceramide synthesis pathway, in hepatocytes. By targeted inhibition of SPTLC2 with lipid nanoparticle\u2013mediated siRNA delivery to hepatocytes, we reduced both hepatic and circulating ceramide levels. This intervention suppressed hepatic lipid uptake and lipogenesis, thereby alleviating MASH progression. Therapeutic efficacy was demonstrated in an 8-week methionine-choline\u2013deficient diet-induced MASH model and validated in a 1-year choline-deficient high-fat diet\u2013induced MASH model. Our findings highlight hepatocyte Sptlc2<\/i> as a promising therapeutic target for MASH.<\/p>\n

Full Article:\u00a0https:\/\/www.science.org\/doi\/10.1126\/sciadv.adx2681<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Abstract Increasing evidence implicates ceramides in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). However, the therapeutic potential of liver-targeted ceramide lowering remains unclear. In this study, we demonstrate that elevated ceramide levels in MASH patients and mouse models are closely associated with the activation of hepatic de novo ceramide synthesis. The analysis of human hepatic […]<\/p>\n","protected":false},"author":9345,"featured_media":3332,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[5],"tags":[],"class_list":["post-3331","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"acf":[],"yoast_head":"\nTargeted inhibition of hepatic de novo ceramide synthesis ameliorates MASH - Pharmacology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/targeted-inhibition-of-hepatic-de-novo-ceramide-synthesis-ameliorates-mash\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Targeted inhibition of hepatic de novo ceramide synthesis ameliorates MASH - Pharmacology\" \/>\n<meta property=\"og:description\" content=\"Abstract Increasing evidence implicates ceramides in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). However, the therapeutic potential of liver-targeted ceramide lowering remains unclear. In this study, we demonstrate that elevated ceramide levels in MASH patients and mouse models are closely associated with the activation of hepatic de novo ceramide synthesis. 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