{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:10:42Z","timestamp":1789992642988,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp; Nutrition"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The identification of direct molecular targets for bioactive dietary components is critical for precision nutrition intervention in metabolic dysfunction\u2010associated steatotic liver disease (MASLD). Fucoxanthin, a marine carotenoid from\n                    <jats:italic>Sargassum fusiforme<\/jats:italic>\n                    , exhibits potent lipid\u2010lowering effects; however, its precise intracellular targets and upstream regulatory mechanisms remain elusive. Herein, using drug affinity responsive target stability (DARTS) coupled with LC\u2013MS\/MS, we identified the endoplasmic reticulum (ER) chaperone glucose\u2010regulated protein 78 (GRP78) as a direct binding target of fucoxanthin. Molecular dynamics (MD) simulations and cellular thermal shift assays (CETSA) confirmed a stable interaction, primarily driven by hydrogen bonding at the ARG74 residue. In\n                    <jats:italic>ob\/ob<\/jats:italic>\n                    mice and palmitic acid\u2010induced HepG2 cells, fucoxanthin treatment significantly alleviated hepatic steatosis and suppressed ER stress. Mechanistically, the fucoxanthin\u2010GRP78 interaction was found to be indispensable for the subsequent activation of AMP\u2010activated protein kinase (AMPK) signaling. Notably, siRNA\u2010mediated knockdown of GRP78 or pharmacological inhibition of AMPK completely abolished the lipid\u2010lowering and ER stress\u2010relieving effects of fucoxanthin, confirming a causal GRP78\u2010AMPK axis. This study elucidates a novel target\u2010driven mechanism wherein fucoxanthin acts as a GRP78 ligand to restore ER homeostasis and reprogram lipid metabolism. These findings position the fucoxanthin\u2010GRP78 axis as a specific therapeutic target for nutritional strategies against MASLD.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71813","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:36:44Z","timestamp":1777538204000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fucoxanthin Ameliorates\n                    <scp>MASLD<\/scp>\n                    by Directly Targeting\n                    <scp>GRP78<\/scp>\n                    to Restore\n                    <scp>ER<\/scp>\n                    Homeostasis and Activate\n                    <scp>AMPK<\/scp>\n                    Signaling"],"prefix":"10.1002","volume":"14","author":[{"given":"Lin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Qionghai People's Hospital  Qionghai China"},{"name":"Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science Wenzhou University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science Wenzhou University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science Wenzhou University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science Wenzhou University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Qionghai People's Hospital  Qionghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2551-4685","authenticated-orcid":false,"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Xianghu Laboratory  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshun","family":"Wen","sequence":"additional","affiliation":[{"name":"Xianghu Laboratory  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Ward, Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7645-3458","authenticated-orcid":false,"given":"Haibin","family":"Tong","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science Wenzhou University  Wenzhou China"},{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao\u2010di Herbs  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases The Third Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177509"},{"issue":"1","key":"e_1_2_10_3_1","first-page":"10","article-title":"Pathogenesis of MASLD and MASH \u2010 Role of Insulin Resistance and Lipotoxicity","volume":"59","author":"Bansal S. 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