Multiomics Reveal the Effects and Regulatory Mechanism of Naringin on Metabolic Dysfunction‐Associated Fatty Liver Disease of Laying Hens

ABSTRACT This study aimed to utilize aged laying hens as a model to investigate the effects of naringin on the occurrence and progression of metabolic dysfunction‐associated fatty liver disease (MAFLD), along with its underlying regulatory mechanisms. A total of 288 aged laying hens, 50‐week‐old, were divided into four groups: a normal diet (ND) group, and three naringin groups receiving 200 mg/kg (N1), 400 mg/kg (N2), and 600 mg/kg (N3). The experiment lasted for 10 weeks, after which serum, liver, and cecal contents were collected from the hens. Results indicated that dietary naringin supplementation reduced hepatic lipid deposition, lowered blood lipid levels, improved antioxidant capacity, and promoted estradiol secretion. Additionally, 16S rDNA analysis revealed that naringin enhanced microbial diversity in the cecum and regulated the abundance of gut microbes associated with fatty liver. Untargeted metabolomics of blood demonstrated that naringin decreased the concentration of glycerophospholipid and sterol lipid metabolites while increasing levels of pantothenic acids and amino acid metabolites. Furthermore, liver transcriptome analysis indicated that naringin interfered with fatty acid synthesis and transport processes while enhancing fatty acid oxidation. Dietary naringin supplementation can mitigate the occurrence of MAFLD by regulating the gut–liver axis and estrogen signaling, particularly in postmenopausal women.