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), TM-challenged (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.

To Cite This Article: Yao Y, Shao L, Zhai P, Yang J, Li J, Zhang X and Qin F, 2026. Quercetin ameliorates tunicamycin-induced hepatic endoplasmic reticulum stress and steatosis involving the g protein-coupled estrogen receptor pathway in rabbits. Pak Vet J, 46(8): 2118-2127. http://dx.doi.org/10.29261/pakvetj/2026.188