LINC01705 derived from adipocyte exosomes regulates hepatocyte lipid accumulation via an miR-552-3p/LXR axis.

High glucose increases the accumulation of lipid droplets in hepatocytes, which eventually results in nonalcoholic fatty liver disease in patients with diabetes. However, the specific mechanism or communication between adipocyte and hepatocyte lipid metabolism is still ambiguous. In this study, exosomes released from human adipocytes were isolated and identified by their morphology, size, and marker proteins by using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting (WB). Gene expression was detected by qRT-PCR and WB. Lipid accumulation was determined by oil red O staining and analyses of total cholesterol (TC) and triglyceride (TG) content. Our results showed that co-culture of HepG2 cells with adipocytes under high glucose conditions stimulated lipid deposition and LINC01705 expression in the HepG2 cells. Exosomes extracted from adipocytes cultured under high glucose conditions had higher levels of LINC01705 than exosomes extracted from adipocytes cultured under normal glucose conditions. Moreover, LINC01705 expression was also elevated in exosomes extracted from diabetes patients when compared with exosomes isolated from normal volunteers, and exosomes from patients who had diabetes complicated with fatty liver (DCFL) had the highest levels of LINC01705 expression. Treatment of HepG2 cells with exosomes extracted from high glucose-stimulated adipocytes promoted lipid deposition and LINC01705 expression in HepG2 cells. Further experiments showed that overexpression of LINC01705 promoted HepG2 lipid metabolism, while inhibition of LINC01705 had the opposite effect. Mechanistically, LINC01705 competitively bound to miR-552-3p, and treatment with miR-552-3p inhibitor reversed the effects induced by LINC01705 knockdown. Moreover, miR-552-3p was found to regulate the transcription activity of LXRα and thereby modulate lipid metabolism-related gene expression. When taken together, our findings showed that high glucose increased the LINC01705 levels in adipocyte exosomes, and thereby improved HepG2 lipid accumulation via an miR-552-3p/LXR axis.