Genistein activated AMPK-SIRT1/PGC-1α pathway through adiponectin and estrogen receptor β signaling to suppress fat deposition in broiler chickens

ABSTRACT Genistein can be used as a dietary additive to control fat deposition in animals, while its mechanism is poorly understood. In this study, a total of 144 male broilers were randomly divided into four groups. Birds were fed standard diets supplemented with 0, 50, 100 or 150 mg of genistein/kg from 21 to 42 days of age. Results showed that genistein treatment decreased the relative weight of abdominal fat and triglyceride contents in broiler chickens. Genistein down-regulated hepatic lipid droplets accumulation and up-regulated the activity of lipoprotein lipase and hepatic lipase and the concentration of adiponectin. Furthermore, the liver X receptor α (LXRα), sterol regulatory element-binding protein 1c (SREBP-1c), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) mRNA expressions were decreased, while the adiponectin receptor 2 (AdipoR2), peroxisome proliferator-activated receptor α (PPARα), adipose triglyceride lipase (ATGL) and carnitine palmitoyl transferase-I (CPT-I) mRNA abundances were increased in the liver of broilers treated with genistein. In addition, genistein increased the NAD+ concentration and NAD+/NADH ratio in the liver. Genistein increased estrogen receptor β (ERβ), forkhead box O1 (FOXO1), nicotinamide phosphoribosyl transferase (Nampt), sirtuin1 (SIRT1), phospho (p)-AMPK, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), p-ACC and CPT-I protein levels, while the SREBP-1c and FAS levels were decreased. These data indicated that genistein might reduces fat accumulation in broiler chickens via activating the AMPK-SIRT1/PGC-1α signaling pathway. The activation of this signaling pathway might be achieved by its direct effect on improving the adiponectin secretion or its indirect effect on up-regulation ERβ expression level through paracrine-acting of adiponectin.