Aim
Glucagon-like peptide-1 receptor agonists (GLP-1Ras) have been reported to prevent non-alcoholic fatty liver disease (NAFLD), but the potential mechanisms are still debated. MicroRNAs (miRNAs) play a prominent role in the field of metabolic disorders, including NAFLD. Our study was designed to further evaluate the effect of GLP-1Ra liraglutide on NAFLD in terms of miRNAs.
Conclusions
MicroRNA-124a overexpression contributes to the progression of NAFLD through reduction of ATGL expression, whereas miR-124a knockdown can reverse this trend, suggesting that miR-124a and its downstream target ATGL can be novel therapeutic targets of NAFLD. We reveal a novel mechanism by which liraglutide attenuates NAFLD by the miR-124a/ATGL/Sirt1 pathway.
Methods
MicroRNA expression was evaluated by clustering analysis of microRNA arrays in high fat diet-fed mice. The luciferase reporter assay was carried out to validate the cross-talk between adipose triglyceride lipase (ATGL) and miR-124a. MicroRNA-124a mimics and inhibitor plasmids were transfected to study the role of miR-124a in palmitate-treated normal human liver cell line (HL-7702). Liraglutide treatment was used to observe the effect of GLP-1Ra on the miR-124a/ATGL pathway.
Results
Expression of ATGL decreased and miR-124a expression increased in hepatosteatosis in vivo and in vitro. Mechanistically, miR-124a interacted with the 3'-untranslated region of ATGL mRNA and induced its degradation. MicroRNA-124a overexpression antagonized the effect of liraglutide on NAFLD by inhibiting ATGL expression, whereas miR-124a knockdown led to elevated ATGL and sirtuin 1 (Sirt1) expression, and subsequently decreased lipid accumulation and inflammation in cells. Conclusions: MicroRNA-124a overexpression contributes to the progression of NAFLD through reduction of ATGL expression, whereas miR-124a knockdown can reverse this trend, suggesting that miR-124a and its downstream target ATGL can be novel therapeutic targets of NAFLD. We reveal a novel mechanism by which liraglutide attenuates NAFLD by the miR-124a/ATGL/Sirt1 pathway.