earticle

영어

Glucosamine (GlcN) is the amino sugar that increases the protein O-GlcNAcylation level by going into the hexosamine biosynthesis pathway (HBP pathway). Previous studies have reported that GlcN regulates autophagy in various organs including the brain, cartilage, and retina. However, its regulating mechanism and role in the liver are still unclear. Here, we observed glucosamine induces autophagy in human hepatocytes (HepG2). Moreover, LC3, one of the most important factors of autophagy, was upregulated by GlcN at the transcriptional and protein levels. We hypothesized that the HBP pathway is involved in GlcN-induced autophagy. Therefore, examined with inhibition of two enzymes, O-GlcNacase and O-GlcNAc transferase, which have an opposite role in the HBP pathway. As a result, the autophagy process was regulated by O-GlcNAcylation levels. To provide the role of GlcN in the liver autophagy process, we conducted the GlcN effect on the fatty liver, known autophagy disrupted disease. Palmitic acid (PA) induced autophagy inhibition and fat accumulation was relieved by GlcN in HepG2 cells. In addition, high-fat diet-induced fatty liver was restored by GlcN through autophagy in mice. Our results indicate that GlcN increased autophagy flux and through this, lipid accumulation can be restored both in vivo and in vitro.