[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-414824-105":59,"doc-detail-414824-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","the-multifaceted-roles-of-ketones-in-physiology","The multifaceted roles of ketones in physiology","","Ketone production (ketogenesis) is essential for maintaining whole-body energy homeostasis during prolonged fasting or starvation. Ketones primarily support neuronal ATP production and can reduce muscle wasting, while other oxidative organs such as the heart and skeletal muscle can also metabolize ketones. Ketones additionally fuel exercising muscle and function as signalling molecules, acting as ligands for GPCRs and modulating gene expression through DNA post-translational modifications. Dysregulated ketone metabolism contributes to cardiometabolic pathologies, with strong evidence in heart failure and type 2 diabetes, motivating a review of therapeutic potential.",{"@graph":69,"@context":123},[70,84,106],{"@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/the-multifaceted-roles-of-ketones-in-physiology/414824/",{"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/the-multifaceted-roles-of-ketones-in-physiology/414824.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is ketogenesis and why is it important during fasting or starvation?","Question",{"text":113,"@type":114},"Ketogenesis is the production of ketones. It helps maintain energy homeostasis during prolonged fasting by supporting neuronal ATP production and limiting muscle wasting.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Besides energy supply, what signalling roles do ketones have?",{"text":118,"@type":114},"Ketones act as ligands for G-protein coupled receptors and can influence gene expression by regulating DNA post-translational modifications.",{"name":120,"@type":111,"acceptedAnswer":121},"How is altered ketone metabolism linked to disease?",{"text":122,"@type":114},"Perturbations in ketone metabolism can contribute to cardiometabolic diseases, with especially strong evidence related to heart failure and type 2 diabetes.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},414824,1790781540,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?_k=1776742907772140068","DOI: 10.1113/EP092243  \nREVIEW ARTICLE  \nThe multifaceted roles of ketones in physiology  \nSeyed Amirhossein Tabatabaei Dakhili1, 2, 3  Kunyan Yang1, 2, 3  Magnus J. Stenlund1, 2, 3  John R. Ussher1, 2, 3   \n1 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada  \n2Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada  \n3 Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada  \nCorrespondence  \nJohn R. Ussher, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 2–020E Katz Centre for Pharmacy and Health Research, Edmonton, AB T6G 2R3, [Canada. Email:](Canada. Email: jussher@ualberta.ca)[ jussher@ualberta.ca](Canada. Email: jussher@ualberta.ca)  \nFunding information  \nCanadian Government | Canadian Institutes of Health Research (CIHR), Grant/Award Number: 173515; Canada Research Chairs (Chaires de recherche du Canada),  \nGrant/Award Number: CRC 232612  \nHandling Editor: Toby Mundel.  \nAbstract  \nThe production of ketones, referred to as ketogenesis, plays an essential role in maintaining energy homeostasis during prolonged fasting/starvation, which primarily stems from its ability to serve as a fuel source to support neuronal ATP production, thereby limiting muscle wasting. Over the years, the field has come to appreciate that ketones are much more than just a fuel source supporting neuronal metabolism, as many other oxidative organs, such as the heart and skeletal muscle, are capable of metabolizing ketones. Furthermore, ketones appear to be an important fuel source for exercising muscle. Beyond supporting ATP production, it is also becoming widely recognized that ketones are powerful signalling molecules, as they serve as ligands for G-protein coupled receptors and can even modify gene expression via regulating DNA post-translational modifications. As they playa key role in supporting whole-body physiology, it is not surprising that perturbations in ketone metabolism can contribute to various pathologies, particularly in relation to cardiometabolic diseases. Some of the strongest evidence supporting the aforementioned statement is seen for both heart failure and type 2 diabetes. Accordingly, we will review herein the multifaceted roles of ketones in supporting whole-body physiology, while interrogating the evidence to suggest whether modifying ketone metabolism may have a therapeutic role in the management of heart failure and type 2 diabetes.  \nKEYWORDS  \nheart failure, ketogenesis, ketone oxidation, ketones, type 2 diabetes  \n1  INTRODUCTION  \nKetones comprise β-hydroxybutyrate (βOHB), acetoacetate and acetone, which were first identified in the urine of diabetic coma patients at the end of the 19th century, leading to ketones being originally viewed as wasteful products of incomplete fatty acid oxidation in the liver (Puchalska & Crawford, 2017; Robinson & Williamson, 1980). Despite these initial derogatory views of  \nketones, seminal studies in the 1960s in starved human participants demonstrated that ketones become the major fuel supporting ATP production in neurons of the brain, illustrating that ketones are essential to normal physiology (Owen et al., 1967). The metabolism of ketones as an alternative fuel source for the brain during times of limited carbohydrate availability (e.g., prolonged fasting) is now regarded as foundational to human physiology, given that neurons lack the enzymatic machinery required to oxidize fatty acids. Thus,  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2025 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.  \n2  \nTABATABAEI DAKHILI ET AL.  \nthe field’s appreciation and knowledge of ketones as an oxidative fuel source to support whole-body metabolism ha","cbCaii1RqRVEBUqT","https://ap.wps.com/l/cbCaii1RqRVEBUqT","pdf",705140,13,"English","# Abstract\n# Introduction\n# Ketone Metabolism During Fasting/Starvation","[{\"question\":\"What is ketogenesis and why is it important during fasting or starvation?\",\"answer\":\"Ketogenesis is the production of ketones. It helps maintain energy homeostasis during prolonged fasting by supporting neuronal ATP production and limiting muscle wasting.\"},{\"question\":\"Besides energy supply, what signalling roles do ketones have?\",\"answer\":\"Ketones act as ligands for G-protein coupled receptors and can influence gene expression by regulating DNA post-translational modifications.\"},{\"question\":\"How is altered ketone metabolism linked to disease?\",\"answer\":\"Perturbations in ketone metabolism can contribute to cardiometabolic diseases, with especially strong evidence related to heart failure and type 2 diabetes.\"}]","The multifaceted roles of ketones in physiology | PDF",1790598809,33]