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A previous study showed that conjugated linoleic acids (CLA) alleviated estrogen-induced FLHS in chickens, but the mechanism remains unclear. In the present study, we found that CLA improved serum lipid homeostasis, reduced hepatic lipid accumulation, and enhanced antioxidant activity in FLHS chickens. Transcriptome analysis identified differentially expressed genes enriched in inflammatory response, lipid homeostasis, carbohydrate metabolism, and mitogen-activated protein kinase (MAPK)\/peroxisome proliferator-activated receptor (PPAR)\/insulin signaling pathways. Metabolome analysis detected differentially abundant metabolites enriched in bile secretion, thyroid hormone synthesis, the insulin signaling pathway, and glycerophospholipid metabolism. Integrated analyses revealed that CLA reshaped the hepatic metabolic profile by upregulating protective metabolites (such as ubiquinol) and downregulating pro-inflammatory\/lipogenic metabolites (such as 15-hydroperoxyeicosa-8Z,11Z,13E-trienoate), which synergized with key gene regulation (fatty acid synthase, jun proto-oncogene, and fatty acid desaturase 2) and core pathway activity (MAPK\/nuclear factor kappa-B inhibition, PPAR\u03b1 activation). The multi-omics study using an estradiol-induced rooster FLHS model elucidated the molecular regulatory network of CLA against hepatic steatosis and liver injury, and provided preliminary mechanistic clues for developing CLA functional additives to prevent and treat FLHS in commercial laying hens.<\/jats:p>","DOI":"10.3390\/ani16172773","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:20:43Z","timestamp":1788427243000},"page":"2773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Conjugated Linoleic Acid Alleviates Hepatic Steatosis and Liver Damage in Estradiol-Induced FLHS Roosters by Reshaping Lipid Metabolism and Inhibiting the MAPK\/NF-\u03baB-Mediated Inflammation Cascade"],"prefix":"10.3390","volume":"16","author":[{"given":"Xuelan","family":"Liu","sequence":"first","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China"},{"name":"Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China"},{"name":"Jinan Key Laboratory of Poultry Germplasm Resources Innovation and Healthy Breeding, Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Heng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China"},{"name":"Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China"},{"name":"Jinan Key Laboratory of Poultry Germplasm Resources Innovation and Healthy Breeding, Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"}]},{"given":"Qingtao","family":"Gao","sequence":"additional","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China"},{"name":"Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China"},{"name":"Jinan Key Laboratory of Poultry Germplasm Resources Innovation and Healthy Breeding, Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2683-4817","authenticated-orcid":false,"given":"Yan","family":"Shang","sequence":"additional","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China"},{"name":"Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China"},{"name":"Jinan Key Laboratory of Poultry Germplasm 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Healthy Breeding, Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"}]},{"given":"Chunyan","family":"Fu","sequence":"additional","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China"},{"name":"Shandong Provincial Key Laboratory of Livestock and Poultry Breeding, Jinan 250100, China"},{"name":"Jinan Key Laboratory of Poultry Germplasm Resources Innovation and Healthy Breeding, Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101320","DOI":"10.1016\/j.psj.2021.101320","article-title":"Untargeted 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