Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes

调节 AMPK 活性和肝脂肪变性的化合物会影响维持肝细胞脂质稳态所需的 microRNA 的生物合成

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作者:Jèssica Latorre, Francisco J Ortega, Laura Liñares-Pose, José M Moreno-Navarrete, Aina Lluch, Ferran Comas, Núria Oliveras-Cañellas, Wifredo Ricart, Marcus Höring, You Zhou, Gerhard Liebisch, P A Nidhina Haridas, Vesa M Olkkonen, Miguel López, José M Fernández-Real0

Background

While the impact of metformin in hepatocytes leads to fatty acid (FA) oxidation and decreased lipogenesis, hepatic microRNAs (miRNAs) have been associated with fat overload and impaired metabolism, contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD).

Methods

We investigated the expression of hundreds of miRNAs in primary hepatocytes challenged by compounds modulating steatosis, palmitic acid and compound C (as inducers), and metformin (as an inhibitor). Then, additional hepatocyte and rodent models were evaluated, together with transient mimic miRNAs transfection, lipid droplet staining, thin-layer chromatography, quantitative lipidomes, and mitochondrial activity, while human samples outlined the translational significance of this work. Findings: Our

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