{"id":56541,"date":"2026-04-20T09:53:03","date_gmt":"2026-04-20T16:53:03","guid":{"rendered":"https:\/\/www.salk.edu\/?post_type=disclosure&#038;p=56541"},"modified":"2026-04-20T13:20:31","modified_gmt":"2026-04-20T20:20:31","slug":"how-the-internal-liver-clock-orchestrates-daily-fat-secretion","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/how-the-internal-liver-clock-orchestrates-daily-fat-secretion\/","title":{"rendered":"How the internal liver clock orchestrates daily fat secretion"},"content":{"rendered":"<ul style=\"margin-bottom: 30px;\">\n<li style=\"list-style: none; padding-left: -20px !important; margin-left: -20px !important;\"><strong>Highlights<\/strong><\/li>\n<li>Metabolic dysfunction-associated steatotic liver disease (MASLD) is among the most common chronic liver diseases, and, when untreated, can progress to cancer, cardiovascular disease, and diabetes<\/li>\n<li>The liver secretes fat into the bloodstream on a precise daily schedule to fuel peripheral tissues and prevent fat accumulation, as seen in MASLD<\/li>\n<li>Salk Institute scientists found that production of a protein called FGF1 in the liver varies throughout the day to affect fat release timing from the liver into the bloodstream, acting as a circadian pacemaker for liver fat metabolism<\/li>\n<li>These findings illuminate a previously unknown circadian lipid trafficking mechanism in the liver, with implications for understanding how disrupted body clocks drive metabolic disease<\/li>\n<\/ul>\n<p>LA JOLLA\u2014Every day, the liver packages fat and releases it into the bloodstream to fuel the body, supplying energy to the heart, muscles, and other organs during the active hours of the day. The liver does not release fat into the bloodstream at random. Like much of human physiology, this daily export of fat follows a precise rhythm, timed to the body\u2019s internal clock. But what molecular signal tells the liver when to act?<\/p>\n<p>A new Salk Institute study identifies a surprising answer: Fibroblast Growth Factor 1 (FGF1), a protein whose production in the liver rises and falls on a daily schedule to trigger a daily pulse of fat release from the liver. In other words, the liver uses FGF1 signaling to time the export of fat to provide energy to tissues such as the heart and muscles when they need it most.<\/p>\n<p>If FGF1 sets this essential clock, then what happens in FGF1\u2019s absence? Fat accumulates in the liver, setting the stage for MASLD.<\/p>\n<p>The findings, published by <a href=\"https:\/\/www.nature.com\/articles\/s41467-026-70849-7#Abs1\" target=\"_blank\" rel=\"noopener\"><em>Nature Communications<\/em><\/a> on March 19, 2026, shed light on how liver fat secretion is regulated in healthy physiology, and what goes wrong in MASLD and other metabolic disorders.<\/p>\n<figure id=\"attachment_56542\"  class=\"wp-caption alignright\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"344\" class=\"img-responsive wp-image-56542 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-458x344.jpg\" alt=\"Jocelyn Torres (left), Benan Pelin Sermikli (center left), Ronald Evans (center), Sihao Liu (center right), and Weiwei Fan (right), and team discovered that the protein FGF1 acts as a circadian timekeeper for liver fat secretion, informing future therapeutic strategies for metabolic and liver diseases.\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-458x344.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-300x225.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-1024x768.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-768x576.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-1536x1152.jpg 1536w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-16x12.jpg 16w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-147x110.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-585x439.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-553x415.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-750x563.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-767x575.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors-945x709.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors.jpg 2000w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><\/a><figcaption class=\"wp-caption-text\">Jocelyn Torres (left), Benan Pelin Sermikli (center left), Ronald Evans (center), Sihao Liu (center right), and Weiwei Fan (right), and team discovered that the protein FGF1 acts as a circadian timekeeper for liver fat secretion, informing future therapeutic strategies for metabolic and liver diseases.<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/04\/260420-pr-evans-authors.jpg\" target=\"_blank\" rel=\"noopener\">\u70b9\u51fb\u6b64\u5904<\/a> \u7528\u4e8e\u9ad8\u5206\u8fa8\u7387\u56fe\u50cf\u3002.<br \/>\u7248\u6743\uff1a\u8428\u514b\u7814\u7a76\u6240<\/figcaption><\/figure>\n<p>\u201cWe knew that liver fat metabolism follows a circadian rhythm, but the molecular logic connecting the clock to that output was unclear,\u201d says study senior and co-corresponding author <a href=\"https:\/\/www.salk.edu\/zh\/scientist\/ronald-evans\/\" target=\"_blank\" rel=\"noopener\">\u7f57\u7eb3\u5fb7\u00b7\u57c3\u6587\u65af\u535a\u58eb<\/a>, professor and holder of the March of Dimes Chair in Molecular and Developmental Biology at Salk. \u201cFGF1 turned out to be a key timekeeper\u2014a signal the liver uses to coordinate when and how much fat it secretes.\u201d<\/p>\n<p>The Salk team, led by co-first authors Benan Pelin Sermikli, PhD, and Sihao Liu, PhD, showed that FGF1 is an output of the liver\u2019s internal clock, continuing to rise and fall each day even when feeding schedules and light cues are removed. FGF1 works by binding to a receptor on the surface of liver cells, setting off a chain reaction inside the cell, including, surprisingly, affecting a protein normally known as a cellular stress sensor that ultimately tells the liver to package and release fat into the bloodstream.<\/p>\n<p>&#8220;This was unexpected,&#8221; says Sermikli, a postdoctoral researcher in Evans\u2019s lab. &#8220;We&#8217;re used to thinking of this cellular sensor as a distress signal. Seeing it activated as part of a normal, daily rhythm reframes how we think about its role in metabolic health.&#8221;<\/p>\n<p>To test what happens without FGF1, the team deleted it specifically in the liver. The daily rhythm of fat secretion disappeared, leading to fat accumulation and accelerated disease in mouse models. What\u2019s more, when MASLD had already developed, adding FGF1 back stalled disease progression.<\/p>\n<p>The findings illustrate a broader principle: Pinpointing the molecular signals that govern normal physiology, in this case the daily rhythm of fat export from the liver, can expose new vulnerabilities in disease and guide future therapies.<\/p>\n<p>\u201cThis research builds on an emerging picture of FGF1 as a systemic lipid trafficker,\u201d says co-corresponding author Michael Downes, a senior staff scientist in Evans\u2019s lab.<\/p>\n<p>The work may also help explain why circadian disruption, from shift work to chronic sleep loss, has been linked to metabolic disease. Each mechanistic step uncovered brings the field closer to therapies grounded not just in symptom management, but in the fundamental biology of how the body regulates fat.<\/p>\n<h2 style=\"font-size: 20px; margin-top: 40px;\"><strong>Other authors and funding<\/strong><\/h2>\n<p>Other authors include Kyeongkyu Kim, Linnea Hases, Ashley Untereiner, Jocelyn Torres, Mingxiao He, Lillian Crossley, Yang Dai, Jonathan Zhu, Chandra Lekha Koopari, Weiwei Fan, Morgan Truitt, Annette Atkins, Michael Downes, and Ronald Evans of Salk; and Tim van Zutphen and Johan Jonker of University of Groningen.<\/p>\n<p>This study was funded by the National Institutes of Health (DK057978-45, HL147835, DK057978, DK120515) and Larry L. Hillblom Foundation, Inc. (2021-D-001-NET).<\/p>","protected":false},"featured_media":0,"template":"","faculty":[91],"disease-research":[123],"class_list":["post-56541","disclosure","type-disclosure","status-publish","hentry","faculty-ronald-evans","disease-research-metabolism-and-diabetes"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>How the internal liver clock orchestrates daily fat secretion - Salk Institute for Biological Studies<\/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:\/\/www.salk.edu\/zh\/news-release\/how-the-internal-liver-clock-orchestrates-daily-fat-secretion\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How the internal liver clock orchestrates daily fat secretion - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"Highlights Metabolic dysfunction-associated steatotic liver disease (MASLD) is among the most common chronic liver diseases, and, when untreated, can progress to cancer, cardiovascular disease, and diabetes The liver secretes fat into the bloodstream on a precise daily schedule to fuel peripheral tissues and prevent fat accumulation, as seen in MASLD Salk Institute scientists found that production of a protein called FGF1 in the liver varies throughout the day to affect fat release timing from the liver into the bloodstream, acting as a circadian pacemaker for liver fat metabolism These findings illuminate a previously unknown circadian lipid trafficking mechanism in the liver, with implications for understanding how disrupted body clocks drive metabolic disease LA JOLLA\u2014Every day, the liver packages fat and releases it into the bloodstream to fuel the body, supplying energy to the heart, muscles, and other organs during the active hours of the day. 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