Quercetin Ameliorates Tunicamycin-Induced Hepatic Endoplasmic Reticulum Stress and Steatosis Involving the G Protein-Coupled Estrogen Receptor Pathway in Rabbits

This study evaluated the effects of the natural flavonoid quercetin (QUE) in regulating liver endoplasmic reticulum (ER) stress and hepatic fat accumulation in tunicamycin (TM)-induced rabbits and explored the underlying molecular mechanisms.New Zealand rabbits (n = 96) were subjected to random assignment into four groups, including normal control (NC), QUE-treated (QUE), TMchallenged (TM), and TM-challenged with QUE (TM+QUE).Our findings demonstrate that QUE treatment significantly ameliorated hepatic histopathological steatosis and relieved liver damage in TM-induced rabbits.QUE improved lipid parameters and ameliorated TM-induced hepatic lipid metabolism disorders.Importantly, QUE attenuated TM-induced hepatic ER stress and oxidative damage in TM-induced rabbits.Meanwhile, QUE suppressed excessive proinflammatory cytokine production and restrained the nuclear factor κB (NF-κB) signaling activation in TM-induced rabbits.Furthermore, QUE increased phosphorylation level of AMP-activated protein kinase (AMPK) and enhanced the protein abundance of G protein-coupled estrogen receptor (GPER).Overall, these results reveal that QUE mitigates hepatic steatosis and ER stress involving the GPER/AMPK pathway, thereby alleviating oxidative stress and inflammatory injury, which supports its potential as a promising nutraceutical for preventing hepatic diseases in rabbits.