[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-419141-105":59,"doc-detail-419141-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","at-the-crossroads-of-health-and-disease-consequences-of-fat-in-the-liver","At the Crossroads of Health and Disease - Consequences of Fat in the Liver","","The liver centrally regulates lipid and glucose metabolism, shifting between energy storage and fuel supply in fed and fasting conditions. When metabolic flexibility is lost, hepatic triglycerides accumulate as lipid droplets, driving broader metabolic disruption. Organ cross-talk with adipose tissue, pancreas, and muscle further shapes these transitions. Steatotic liver diseases also increase inflammatory and fibrotic risks, contributing substantially to global morbidity and mortality; this review summarizes mechanisms and clinical therapies for common forms.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/at-the-crossroads-of-health-and-disease-consequences-of-fat-in-the-liver/419141/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/at-the-crossroads-of-health-and-disease-consequences-of-fat-in-the-liver/419141.png","ImageObject",300,407,{"name":92,"@type":93},"Rizky","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does impaired metabolic flexibility contribute to fat accumulation in the liver?","Question",{"text":112,"@type":113},"Loss of the liver’s ability to shift between energy substrates promotes accumulation of hepatic triglyceride as lipid droplets and triggers additional metabolic perturbations.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which organs have important cross-talk with the liver during metabolic transitions?",{"text":117,"@type":113},"Cross-talk during these transitions involves adipose tissue, pancreas, and muscle.",{"name":119,"@type":110,"acceptedAnswer":120},"What risks do steatotic liver diseases pose beyond metabolic consequences?",{"text":121,"@type":113},"They carry significant liver risks through inflammatory and fibrotic processes, increasing the likelihood of steatohepatitis, fibrosis, cirrhosis, and liver cancer.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},419141,1790695805,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962085564807,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Author Manuscript Author Manuscript Author Manuscript Author Manuscript  \n\n| | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>Annu Rev Physiol. Author manuscript; available in PMC 2026 January 02. |\n| --- | --- |\n\nPublished in final edited form as:  \nAnnu Rev Physiol. 2025 February ; 87(1): 325–352. doi:10.1146/annurev-physiol-022724-105515 .  \nAt the Crossroads of Health and Disease: Consequences of Fat in the Liver  \nMatthew Dukewich, Liyun Yuan, Norah A. Terrault  \nDivision of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA  \nAbstract  \nThe liver plays a central role in regulating lipid and glucose metabolism, particularly in transitioning between energy storage and provision in fed and fasting states. Loss of metabolic flexibility, characterized by the impaired capacity to shift between different energy substrates, sets the stage for accumulation of hepatic triglyceride as lipid droplets and further metabolic perturbations. Cross talk between the liver and other organs, including adipose tissue, pancreas, and muscle, is relevant in this transition. In addition to the metabolic consequences of steatosis, there are significant liver risks related to triggered inflammatory and fibrotic processes. Steatotic liver diseases affect an estimated one in three adults globally and contribute to substantial morbidity and mortality. This review focuses on the liver’s role in lipid metabolism, defining metabolic health and unhealth, the pathogenic underpinnings that lead to steatohepatitis and hepatic fibrosis, and the clinical features and therapies for the most common forms of steatotic liver diseases.  \nKeywords  \nmetabolic dysfunction–associated steatotic liver disease; MASLD; alcohol-associated liver disease; ALD; lipogenesis; lipotoxicity; metabolic health  \n1. INTRODUCTION  \nHepatic steatosis is defined by the accumulation offat within hepatocytes, primarily as triglyceride (TG), in greater than 5% of hepatocytes and is remarkably common. Populationbased estimates from the United States, Europe, and Asia suggest that one in three adults has hepatic steatosis (1). Recently changed from fatty liver to steatotic liver disease (SLD), this umbrella term includes metabolic dysfunction–associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, alcohol-associated liver disease (ALD),  \nThis work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.  \n[Terrault@usc.edu](Terrault@usc.edu) .  \nAuthor Manuscript Author Manuscript Author Manuscript Author Manuscript  \nDukewich et al. Page 2  \nan overlap group termed MetALD, and other secondary causes (e.g., mediation associated, viral associated) (2) (Table 1). MASLD is the leading cause of steatotic liver disease, affecting approximately one quarter of the global population. A significant portion of individuals with hepatic steatosis will develop liver inflammation (steatohepatitis) and fibrosis and be at risk for cirrhosis and liver cancer. The tipping point at which liver fat disrupts liver health and overall health is multifaceted and complex. This review focuses on the liver’s role in lipid metabolism, defining metabolic health and unhealth, the pathogenic underpinnings that lead to steatohepatitis and hepatic fibrosis, and the clinical features and therapies for specific steatotic liver diseases.  \n2. LIVER AND NORMAL METABOLISM  \nThe liver plays a central role in regulating lipid and glucose metabolism. Hepatocytes possess remarkable metabolic flexibility in transitioning between tasks of energy storage and provision during fed and fasted states, respectively. During the fasting state, insulin levels are low, and lipolysis is stimulated, leading to the re","cbCaiiD253kUEH8C","https://ap.wps.com/l/cbCaiiD253kUEH8C","pdf",2180316,37,"English","# INTRODUCTION\n# LIVER AND NORMAL METABOLISM","[{\"question\":\"How does impaired metabolic flexibility contribute to fat accumulation in the liver?\",\"answer\":\"Loss of the liver’s ability to shift between energy substrates promotes accumulation of hepatic triglyceride as lipid droplets and triggers additional metabolic perturbations.\"},{\"question\":\"Which organs have important cross-talk with the liver during metabolic transitions?\",\"answer\":\"Cross-talk during these transitions involves adipose tissue, pancreas, and muscle.\"},{\"question\":\"What risks do steatotic liver diseases pose beyond metabolic consequences?\",\"answer\":\"They carry significant liver risks through inflammatory and fibrotic processes, increasing the likelihood of steatohepatitis, fibrosis, cirrhosis, and liver cancer.\"}]","At the Crossroads of Health and Disease - Consequences of Fat in the Liver | PDF",1790615804,93]