Quercetin alleviates endoplasmic reticulum stress and apoptosis through activation of g protein-coupled estrogen receptor signaling in laying hens with fatty liver hemorrhagic syndrome.

The research was conducted to elucidate the regulatory functions and potential mechanism of quercetin (Que) on hepatic steatosis, endoplasmic reticulum (ER) stress, and apoptosis in laying hens with fatty liver hemorrhagic syndrome (FLHS). Healthy Hy-Line Brown laying hens (n = 96) were allocated to four groups, including the normal control (NC) group, the high-energy low-protein (HELP) group, and the HELP diet group supplemented with 200 or 400 mg/kg Que, respectively. The findings indicated that Que administration remarkably relieved hepatic steatosis, ER stress, cell apoptosis, and liver damage in laying hens subjected to HELP diets. Specifically, Que largely reduced serum lipid parameters in HELP-fed laying hens, and alleviated hepatic lipid metabolism disorders by upregulating lipolysis-related factors and downregulating lipogenic-associated factors. In addition, Que mitigated aberrant lipid accumulation, ER stress, and cell apoptosis in primary chicken hepatocytes exposed to palmitic acid (PA) or tunicamycin (TM), a typical inducer of ER stress. Mechanistically, the protective impacts of Que against lipid deposition and ER stress might be mediated through the activation of the G-protein coupled estrogen receptor (GPER) signaling pathway. Overall, Que alleviates FLHS in laying hens through inhibiting ER stress and apoptosis mediated by activation of GPER signaling pathway. These findings reveal novel perspectives on the mechanisms by which Que prevent FLHS progression, and highlights its potential as a feed additive for FLHS prophylaxis in the laying hen industry.