4.7 Article

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, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.798735

Keywords

lipid metabolism; AML-12 cells; Wnt/beta-catenin; FFA; TMEM88

Funding

  1. 512 Talent Cultivation Plan of Bengbu Medical College [by51201313]
  2. Natural Science Foundation of Anhui Province [1808085MH235, 2008085QH401]

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This study clarified the molecular mechanism of TMEM88 in regulating lipid synthesis and metabolism cytokine in non-alcoholic fatty liver disease (NAFLD). The findings suggest that TMEM88 plays a role in the progression of NAFLD through the Wnt/β-catenin signaling pathway in AML-12 cells.
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-alpha, FASN, and ACOX-1 were evaluated by RT-qPCR and Western blotting.Results: The study found that the secretion of PPAR-alpha 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/beta-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/beta-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.

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