Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120/ABHD6

Abstract

Objective Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. Methods Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of α/β hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. Results Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1–6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1–6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1–6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. Conclusion Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD.

Carvacrol improves blood lipid and glucose in rats with type 2 diabetes mellitus by regulating short-chain fatty acids and the GPR41/43 pathway

“…IEC-6 cells were grouped as follows: the control group (5.5 mM glucose), the high glucose (HG) group (30 mM glucose + 1 nM free fatty acid [0.33 mM palmitic acid, 0.67 mM oleic acid] [ 22 ]), the HG + CAR group (cells were treated with 20, 50, 100, 200, 500 µM/ml CAR for 24 h in HG environment [ 16 ]), the HG + CAR + sodium β-hydroxybutyrate (SHB) group (cells were treated with 200 µM/ml CAR and 5 mM SHB simultaneously for 24 h in HG environment [ 23 ]), the HG + CAR + GLPG0974 (GLPG) group (cells were treated with 200 µM/ml CAR and 0.1 µM GLPG simultaneously for 24 h in HG environment [ 23 ]), the HG + SHB + GLPG group (cells were treated with 200 µM/ml CAR, 5 mM SHB and 0.1 µM GPLG simultaneously for 24 h in HG environment [ 23 ]). Among them, SHB, a GPR41 antagonist, was obtained from Sigma-Aldrich; GLPG, a GPR43 antagonist, was purchased from Tocris Bioscience [ 23 ].…”

YTHDC1 aggravates high glucose-induced retinal vascular endothelial cell injury via m6A modification of CDK6

“…Retinal tissue was fixed with 4% neutral formalin and embedded in paraffin. Sections were stained with H&E as per normal procedure [ 16 ]. Histopathological changes were analyzed professionally by pathologists who were not previously aware of the groups.…”