{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:53:36Z","timestamp":1790034816510,"version":"4.0.1"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study elucidates the protective mechanisms of whey protein (WP) in treating high\u2010fat diet (HFD)\u2010induced nonalcoholic fatty liver disease (NAFLD) in mice, emphasizing its role in bile acid regulation, intestinal flora homeostasis, and inflammatory suppression. ICR mice were subjected to a 12\u2010week HFD to establish NAFLD, followed by WP intervention (200\u2009g\/kg). Comprehensive analyses included histopathological assessment (HE staining), serum biomarkers, hepatic gene expression (qPCR), gut microbial profiling (16S rRNA sequencing), quantitative bile acid and short\u2010chain fatty acid (SCFA) analysis, and serum metabolomics. Core targets were predicted via network pharmacology and validated through molecular docking. WP administration markedly alleviated NAFLD progression by targeting multiple pathways: (1) It suppressed hepatic lipid deposition and inflammatory injury, downregulating NLRP3, NF\u2010\u03baB, and TNF\u2010\u03b1 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) while enhancing Nrf2\/HO\u20101\u2010mediated antioxidant defenses; (2) Network pharmacology prioritized IL\u20101\u03b2, STAT3, and MMP9 as pivotal targets, with \u03b2\u2010lactoglobulin exhibiting high binding potentials (STAT3: \u22121.42\u2009kcal\/mol); (3) WP restored gut microbial balance, enriching beneficial taxa (e.g.,\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    ) and fecal SCFAs; (4) It reprogrammed bile acid metabolism, elevating cholesterol\u2010cleaving enzymes (CYP7A1\/CYP27A1) but inhibiting FXR\/SHP (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), alongside increased hepatoprotective bile acids (TDCA\/TUDCA). Metabolomics identified WP\u2010induced anti\u2010inflammatory mediators (e.g., eicosapentaenoic acid) and perturbations in arginine and unsaturated fatty acid pathways, synergistically attenuating steatosis and fibrosis. WP counters NAFLD via a tripartite mechanism: gut microbiome\u2010directed SCFA synthesis, bile acid\u2010driven cholesterol disposal, and dual modulation of inflammation (NLRP3\/NF\u2010\u03baB) and oxidative stress (Nrf2\/HO\u20101). These insights position WP as a promising dietary strategy targeting the gut\u2010liver axis.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71655","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:25:07Z","timestamp":1773721507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multi\u2010Target Mechanisms of Whey Protein Against\n                    <scp>NAFLD<\/scp>\n                    : Integrating Bile Acid Metabolism, Gut Microbiota and Hepatic Inflammation"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4945-9914","authenticated-orcid":false,"given":"Dongjin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Dongtai Hospital of Traditional Chinese Medicine  Yancheng Jiangsu 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