Bax Inhibitor-1 regulates hepatic lipid accumulation via ApoB secretion.
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.
Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju 560-182, Korea.
Hwa Young
HY
Lee
Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju 560-182, Korea.
Geum-Hwa
GH
Lee
Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju 560-182, Korea.
Kashi Raj
KR
Bhattarai
Department of Biochemistry, School of Medicine, Chonbuk National University, Jeonju 560-182, Korea.
Byung-Hyun
BH
Park
Division of Life Sciences, Korea University, 145 Anam-Ro, Seongbuk-Gu, Seoul, 136-713, Korea.
Seung-Hoi
SH
Koo
Department of Dental Pharmacology, School of Dentistry, Wonkwang University, Iksan, 570-749, Korea.
Hyung-Ryong
HR
Kim
Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju 560-182, Korea.
Han Jung
HJ
Chae
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D059305:Diet, High-Fat; D004220:Disulfides / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D005227:Fatty Acids / Q000096:biosynthesis; D005786:Gene Expression Regulation; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D017510:Protein Folding; D017382:Reactive Oxygen Species / Q000378:metabolism
D001055:Apolipoproteins B; D004220:Disulfides; D005227:Fatty Acids; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; C490015:Tmbim6 protein, mouse