Abstract: Abstract: Objective To investigate the effect of salubrinal on obesity-induced non-alcoholic fatty liver disease.
Methods Thirty female C57BL/6 mice were randomly divided into three groups: standard chow diet (SCD) group, high-fat
diet (HF) group and HF with salubrinal (HF+S) group. The HF and HF+S groups were given a high-fat diet (fat content:
60%). After 4-week obesity induction, salubrinal was subcutaneously injected for the next 4 weeks in HF+S group. During
the experiment, the changes in animal body compositions were measured regularly. Serum lipid parameters were examined
through venous blood. The abdominal subcutaneous fat, periuterine and perirenal fat, and liver were collected for wet mass
determination. The pathological changes of the liver tissues were observed by H&E and oil red O staining for investigating
the effect and mechanism of salubrinal on the hepatic steatosis. The expressions of proteins related to eIF2α signaling (Bip,
p-eIF2α, eIF2α, ATF4 and CHOP) were detected by Western blot assay. Results Compared to the SCD group, the serum
lipid level and the fat accumulation were increased in HF and HF+S groups. After treatment with salubrinal, the lipid
disorder was relieved. Also, the histological severity of hepatic steatosis in the liver was suppressed in response to salubrinal.
In addition, Western blot analysis showed that salubrinal inhibited endoplasmic reticulum stress by increasing the
expressions of Bip, p-eIF2α and ATF4 with a decrease level of CHOP. Conclusion Salubrinal can effectively alleviate
obesity and non-alcoholic fatty liver disease and regulate lipid metabolism by altering endoplasmic reticulum stress through
eIF2α signaling.

Key words: non-alcoholic fatty liver disease, obesity, endoplasmic reticulum stress, eukaryotic initiation factor-2;
Salubrinal