FAM172A Deletion May Enhance Hepatic Steatosis by Promoting ER Stress

• Published in: Digestive diseases and sciences 2021-09, Vol.66 (9), p.3054-3061
• Main Authors: Xiao, Fan, Gao, Meixin, Yang, Junru, He, Lingling, Wei, Hongshan
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Apoptosis; Automation; Biochemistry; Cell Line; Cell Proliferation; Cell Survival; Endoplasmic reticulum; Endoplasmic Reticulum - physiology; Endoplasmic Reticulum Stress - genetics; Gastroenterology; Gene Deletion; Gene Expression Profiling - methods; Gene Expression Regulation; Hepatology; Infectious diseases; Kinases; Liver; Liver - metabolism; Liver - pathology; Liver diseases; Medicine; Medicine & Public Health; Mice; Microscopy; Non-alcoholic Fatty Liver Disease - metabolism; Oncology; Original Article; Proteins; Proteins - genetics; Proteins - metabolism; Reagents; Transplant Surgery; Unfolded Protein Response
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-020-06601-y

Background Endoplasmic reticulum (ER) stress is one of the major causes to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Our previous study showed that maintains the homeostasis of ER could effectively alleviate NAFLD. In this study, we found that the loss of FAM172A increased ER stress. Aims The aims of this study were to explore whether FAM172A could improve NAFLD by inhibiting ER stress. Methods The expression levels of FAM172A and ER stress were detected by western blot. The method of immunofluorescence was used to determine FAM172A location. The interacted proteins of FAM172A were identified by immunocoprecipitation. The methods of MTS and caspase-3/7 activity were taken to confirm the effect of FAM172A on cell viability and proliferation. The expression levels of inflammation were detected by qPCR. Results We confirmed that FAM172A might alleviate NAFLD through inhibiting ER stress. Loss of FAM172A increased the expressions of ATF6, peIF2α, but decreased the expression of IRE1α. Then, it was shown that FAM172A located in ER and FAM172A directly interacted with ATF6 and peIF2α and IRE1α. More importantly, the binding of FAM172A and eIF2a in tunicamycin-treated group increased significantly compared with the control group. However, the binding of FAM172A and ATF6 or IRE1α did not change. Next, we found that the lack of FAM172A could produce more apoptosis and inflammation. Conclusions Our results suggest that FAM172A improve steatosis by alleviating ER stress.