OGT contributes to the progression of NAFLD

OGT contributes to the progression of NAFLD. (1) The phosphorylation of uridine increases UDP-GlcNAc levels, which is regulated by ChREBP and SREBP1C, modifying FAS by O-GlcNAcylation, and is later increased by an interaction with USP2A. Meanwhile, the increase in UDP-GlcNAc also modifies FOXO1 by O-GlcNAcylation, alters gluconeogenesis, i.e., the insulin pathway, and causes a decrease in FABP1, leading to the formation of NAFLD. In addition, the FAS inhibitor FXR, modified by O-GlcNAcylation, further inhibits the formation of NAFLD. (2) AIMP2 and PARP1 in aging fatty liver are associated with NAD+ levels. Higher levels of NAD+ increase the activity of SIRT1 and SIRT3, which can protect hepatocytes. (3) Excessive fat accumulation leads to the accumulation of ROS, triggers ER stress, and increases the expression of GFAT and OGT. XBP1 and FBPase are also involved in contributing to HBP-mediated inflammation. Of importance, curcumin and silibinin exert their anti-inflammatory effects by regulating the XBP1-related pathway as well as the expression of OGT

Publication

Biological Functions and Potential Therapeutic Significance of O-GlcNAcylation in Hepatic Cellular Stress and Liver Diseases (2024) Zun Mao, et al. Cells. 2024 May;13(10). Figure: F3. Homo sapiens

Disease mentions