TY - JOUR
T1 - Sterol O-acyltransferase 2 chaperoned by apolipoprotein J facilitates hepatic lipid accumulation following viral and nutrient stresses
AU - Sun, Hung Yu
AU - Chen, Tzu Ying
AU - Tan, Yu Ching
AU - Wang, Chun Hsiang
AU - Young, Kung Chia
N1 - Funding Information:
The authors would like to thank the Ministry of Science and Technology of Taiwan (104-2320-B-006-017-MY3, 107-2320-B-006-031-MY3, and 108-2320-B-006-039-MY3), National Cheng Kung University and Show Chwan Health Care System Program (NCKUSCMH10604, NCKUSCMH10708, and NCKUSCMH10807), NSFC grant (No. 81971940), and the Fundamental Research Funds for the Central Universities (No. 531118010216) for financially supporting this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We also thank the technical services provided by the “Bio-image Core Facility of the National Core Facility Program for Biotechnology, Ministry of Science and Technology, Taiwan” and Enya Hsiao for her English editing.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - The risks of non-alcoholic fatty liver disease (NAFLD) include obese and non-obese stresses such as chronic hepatitis C virus (HCV) infection, but the regulatory determinants remain obscure. Apolipoprotein J (ApoJ) served as an ER-Golgi contact-site chaperone near lipid droplet (LD), facilitating HCV virion production. We hypothesized an interplay between hepatic ApoJ, cholesterol esterification and lipid deposit in response to NAFLD inducers. Exposures of HCV or free-fatty acids exhibited excess LDs along with increased ApoJ expression, whereas ApoJ silencing alleviated hepatic lipid accumulation. Both stresses could concomitantly disperse Golgi, induce closer ApoJ and sterol O-acyltransferase 2 (SOAT2) contacts via the N-terminal intrinsically disordered regions, and increase cholesteryl-ester. Furthermore, serum ApoJ correlated positively with cholesterol and low-density lipoprotein levels in normal glycaemic HCV patients, NAFLD patients and in mice with steatosis. Taken together, hepatic ApoJ might activate SOAT2 to supply cholesteryl-ester for lipid loads, thus providing a therapeutic target of stress-induced steatosis.
AB - The risks of non-alcoholic fatty liver disease (NAFLD) include obese and non-obese stresses such as chronic hepatitis C virus (HCV) infection, but the regulatory determinants remain obscure. Apolipoprotein J (ApoJ) served as an ER-Golgi contact-site chaperone near lipid droplet (LD), facilitating HCV virion production. We hypothesized an interplay between hepatic ApoJ, cholesterol esterification and lipid deposit in response to NAFLD inducers. Exposures of HCV or free-fatty acids exhibited excess LDs along with increased ApoJ expression, whereas ApoJ silencing alleviated hepatic lipid accumulation. Both stresses could concomitantly disperse Golgi, induce closer ApoJ and sterol O-acyltransferase 2 (SOAT2) contacts via the N-terminal intrinsically disordered regions, and increase cholesteryl-ester. Furthermore, serum ApoJ correlated positively with cholesterol and low-density lipoprotein levels in normal glycaemic HCV patients, NAFLD patients and in mice with steatosis. Taken together, hepatic ApoJ might activate SOAT2 to supply cholesteryl-ester for lipid loads, thus providing a therapeutic target of stress-induced steatosis.
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U2 - 10.1038/s42003-021-02093-2
DO - 10.1038/s42003-021-02093-2
M3 - Article
C2 - 33980978
AN - SCOPUS:85105797540
VL - 4
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
IS - 1
M1 - 564
ER -