Diet‑inducing hypercholesterolemia show decreased O‑GlcNAcylation of liver proteins through modulation of AMPK.

O-GlcNAcylation, a nutritionally driven, post-translational modification of proteins, is gaining importance because of its
health implications. Changes in O-GlcNAcylation are observed in various disease conditions. Changes in O-GlcNAcylation
by diet that causes hypercholesterolemia are not critically looked into in the liver. To address it, both in vitro and in vivo
approaches were employed. Hypercholesterolemia was induced individually by feeding cholesterol (H)/high-fat (HF) diet.
Global O-GlcNAcylation levels and modulation of AMPK activation in both preventive and curative approaches were looked
into. Diet-induced hypercholesterolemia resulted in decreased O-GlcNAcylation of liver proteins which was associated
with decreased O-linked N-acetylglucosaminyltransferase (OGT) and Glutamine fructose-6-phosphate amidotransferase-1
(GFAT1). Activation of AMPK by metformin in preventive mode restored the O-GlcNAcylation levels; however, metformin
treatment of HepG2 cells in curative mode restored O-GlcNAcylation levels in HF but failed to in H condition (at 24 h).
Further, maternal faulty diet resulted in decreased O-GlcNAcylation in pup liver despite feeding normal diet till adulthood.
A faulty diet modulates global O-GlcNAcylation of liver proteins which is accompanied by decreased AMPK activation
which could exacerbate metabolic syndromes through fat accumulation in the liver.