AUTHOR=Zhou Huan , Zhu Xingyu , Yao Yan , Su Yue , Xie Jing , Zhu Minhui , He Cuixia , Ding Jiaxiang , Xu Yuanyuan , Shan Rongfang , Wang Ying , Zhao Xiangdi , Ding Yuzhou , Liu Bingyan , Shao Zhonghuan , Liu Yuanyuan , Xu Tao , Xie Yunqiu
TITLE=TMEM88 Modulates Lipid Synthesis and Metabolism Cytokine by Regulating Wnt/β-Catenin Signaling Pathway in Non-Alcoholic Fatty Liver Disease
JOURNAL=Frontiers in Pharmacology
VOLUME=12
YEAR=2022
URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.798735
DOI=10.3389/fphar.2021.798735
ISSN=1663-9812
ABSTRACT=Objective: To clarify the molecular mechanism of TMEM88 regulating lipid synthesis and metabolism cytokine in NAFLD.
Methods:In vivo, NAFLD model mice were fed by a Methionine and Choline-Deficient (MCD) diet. H&E staining and immunohistochemistry experiments were used to analyze the mice liver tissue. RT-qPCR and Western blotting were used to detect the lipid synthesis and metabolism cytokine. In vitro, pEGFP-C1-TMEM88 and TMEM88 siRNA were transfected respectively in free fat acid (FFA) induced AML-12 cells, and the expression level of SREBP-1c, PPAR-α, FASN, and ACOX-1 were evaluated by RT-qPCR and Western blotting.
Results: The study found that the secretion of PPAR-α and its downstream target ACOX-1 were upregulated, and the secretion of SREBP-1c and its downstream target FASN were downregulated after transfecting with pEGFP-C1-TMEM88. But when TMEM88 was inhibited, the experimental results were opposite to the aforementioned conclusions. The data suggested that it may be related to the occurrence, development, and end of NAFLD. Additionally, the study proved that TMEM88 can inhibit Wnt/β-catenin signaling pathway. Meanwhile, TMEM88 can accelerate the apoptotic rate of FFA-induced AML-12 cells.
Conclusion: Overall, the study proved that TMEM88 takes part in regulating the secretion of lipid synthesis and metabolism cytokine through the Wnt/β-catenin signaling pathway in AML-12 cells. Therefore, TMEM88 may be involved in the progress of NAFLD. Further research will bring new ideas for the study of NAFLD.