In this study, we explored the effects of Bax Inhibitor-1 (BI-1) on ApoB aggregation in high-fat diet (HFD)-induced hepatic lipid accumulation. After 1 week on a HFD, triglycerides and cholesterol accumulated more in the liver and were not effectively secreted into the plasma, whereas after 8 weeks, lipids were highly accumulated in both the liver and plasma, with a greater effect in BI-1 KO mice compared with BI-1 WT mice. ApoB, a lipid transfer protein, was accumulated to a greater extent in the livers of HFD-BI-1 KO mice compared with HFD-BI-1 WT mice. Excessive post-translational oxidation of protein disulfide isomerase (PDI), intra-ER ROS accumulation and folding capacitance alteration were also observed in HFD-BI-1 KO mice. Higher levels of endoplasmic reticulum (ER) stress were consistently observed in KO mice compared with the WT mice. Adenovirus-mediated hepatic expression of BI-1 in the BI-1 KO mice rescued the above phenotypes. Our results suggest that BI-1-mediated enhancement of ApoB secretion regulates hepatic lipid accumulation, likely through regulation of ER stress and ROS accumulation.
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