The exponential increase in the consumption of refined sugar, and more specifically, high fructose corn syrup (HFCS) correlates with the increased incidence of metabolic diseases such as non-alcoholic steatohepatitis (NASH) and certain cancers such as hepatocellular carcinoma (HCC). Recent work from several laboratories, including ours suggests that fructose affects hepatosteatosis through the \u2018gut-liver axis\u2019, a physiological circuit through which gut microbiota and\/or their products reach the liver via the portal circulation to provoke an inflammatory response that alters liver metabolism (1,2). Specifically, we show that that excessive fructose consumption results in gut barrier deterioration, dysbiosis, low-grade intestinal inflammation and endotoxemia, in a pre-clinical model of NASH (1). Using single nucleus RNAseq, we have recently uncovered a novel transcriptional signature in hepatocytes with both diagnostic and prognostic significance for HCC that involves pathways involved in inflammation and ER Stress (3) and that treating preclinical models with drugs that specifically target these pathways can arrest NASH and HCC progression in the absence of altering the liver or blood lipidome (4). These data will be discussed.<\/p>\n
Hosted by Cristina Mu\u00f1oz Pinedo – Preclinical and experimental research in thoracic tumors (PReTT) group<\/em><\/p>\n ___________________<\/p>\n (1) Todoric, J. et al. Fructose stimulated de novo lipogenesis is promoted by inflammation. Nat Metab 2, 1034-1045, (2020).
\n(2) Febbraio, M.A. & Karin, M. “Sweet death”: Fructose as a metabolic toxin that targets the gut-liver axis. Cell Metab, (2021).
\n(3) Carlessi R. et al. Single nucleus RNA sequencing of pre-malignant liver reveals disease associated hepatocyte state with HCC prognostic potential. Cell Genomics (in press 2023).
\n(4) Boslem E. Therapeutic blockade of ER stress and inflammation prevents NASH and progression to HCC. In review.<\/p>\n","protected":false},"featured_media":22515,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"default","ast-site-content-layout":"","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":"","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":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"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-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-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-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-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-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-gradient":""}}},"tags":[78],"_links":{"self":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/agenda\/22514"}],"collection":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/agenda"}],"about":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/types\/agenda"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/media\/22515"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/media?parent=22514"}],"wp:term":[{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/tags?post=22514"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}