Dietary Genistein Alleviates Lipid Metabolism Disorder and Inflammatory Response in Laying Hens With Fatty Liver Syndrome

This study investigated the molecular mechanism underlying the effect of dietary genistein (GEN) on fatty liver syndrome (FLS) in laying hens. Hens in the control group (CG) were fed a high-energy and low-choline (HELC) diet to establish the FLS model. The livers of the FLS hens were friable and swollen from hemorrhage. Hepatic steatosis and inflammatory cell infiltration were present around the liver blood vessels. Hens in the low-genistein (LGE) and high-genistein (he) groups were fed GEN at 40 and 400 mg/kg doses, respectively, as supplements to the HELC diet. GEN at 40 mg/kg significantly increased gonadotropin-releasing hormone (GnRH) mRNA expression in the hypothalamus, the serum estrogen (E2) level, and the laying rate, whereas 400 mg/kg of GEN decreased GnRH expression and the laying rate without significantly affecting E2, suggesting that high-dose GEN adversely affected the reproductive performance. Either high- or low-dose GEN treatment could alleviate metabolic disorders and inflammatory responses in FLS hens. GEN significantly decreased the serum ALT, creatinine, triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA) levels. Accordingly, the TG and long-chain fatty acid (LCFA) levels, including long-chain saturated fatty acids (LSFAs) and monounsaturated fatty acids (MUFAs), and the n-6:n-3 polyunsaturated fatty acid (PUFA) ratio in the liver were reduced after the GEN treatments, whereas the levels of C22:0, n-3 family fatty acids, C20:3n6, and C20:4n6 were increased. These results indicated that dietary GEN downregulated the expression of genes related to fatty acid synthesis [sterol regulatory element-binding protein 1 (SREBP1c), liver X receptor alpha (LXR alpha), fatty acid synthase (FAS), and acetyl coenzyme A synthetase (ACC)] and the fatty acid transporter (FAT). Furthermore, GEN treatments upregulated the transcription of genes related to fatty acid beta-oxidation [peroxisome proliferator-activated receptor (PPAR)alpha, PPAR delta, ACOT8, ACAD8, and ACADs] in the liver and reduced PPAR gamma and AFABP expression in abdominal fat. Dietary GEN alleviated inflammatory cell infiltration in the livers of FLS hens and downregulated TNF-alpha, IL-6, and IL-1 beta expression. Moreover, GEN treatment increased SOD activity and decreased malondialdehyde activity in the liver. In conclusion, GEN supplementation in the feed inhibited fatty acid synthesis and enhanced beta-oxidation in the liver through the PPAR-ACAD/ACOT and PPAR-LXR alpha-SREBP1c-ACC/FAS/FAT pathways. Dietary GEN alleviated metabolic disorder and inflammation in the FLS hens by improving the antioxidant capacity and fatty acid profile.