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In this study, we conducted a comprehensive analysis of a large chicken population consisting of 705 adult hens by combining host genome resequencing; liver transcriptome, proteome, and metabolome analysis; and microbial 16S ribosomal RNA gene sequencing of each gut segment. The results showed the heritability (h2 = 0.25) and duodenal microbiability (m2 = 0.26) of hepatic steatosis were relatively high, indicating a large effect of host genetics and duodenal microbiota on chicken hepatic steatosis. Individuals with hepatic steatosis had low microbiota diversity and a decreased genetic potential to process triglyceride output from hepatocytes, fatty acid \u03b2-oxidation activity, and resistance to fatty acid peroxidation. Furthermore, we revealed a molecular network linking host genomic variants (GGA6: 5.59\u20135.69 Mb), hepatic gene\/protein expression (PEMT, phosphatidyl-ethanolamine N-methyltransferase), metabolite abundances (folate, S-adenosylmethionine, homocysteine, phosphatidyl-ethanolamine, and phosphatidylcholine), and duodenal microbes (genus Lactobacillus) to hepatic steatosis, which could provide new insights into the regulatory mechanism of fatty liver development.<\/jats:p>","DOI":"10.1093\/gigascience\/giae023","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T19:35:45Z","timestamp":1717616145000},"source":"Crossref","is-referenced-by-count":12,"title":["Mechanisms of hepatic steatosis in chickens: integrated analysis of the host genome, molecular phenomics and gut microbiome"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9673-9533","authenticated-orcid":false,"given":"Congjiao","family":"Sun","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University , Beijing 100193 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9637-7762","authenticated-orcid":false,"given":"Fangren","family":"Lan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding, Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University , Beijing 100193 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