Abstract: Objective To investigate the changes in the functional activity of glycogen synthase kinase-3 (GSK-3) in the hepatic
tissue after endotoxin (lipopolysaccharide, LPS) tolerance and explore the effects of LPS-induced GSK-3 inhibition on glycogen
metabolism in the liver. Methods Male SD rats were randomly divided into normal control, endotoxin pretreatment and
GSK-3 inhibitor (lithium chloride) groups with corresponding pretreatments prior to a large dose of LPS challenge (10 mg/kg)
to induce liver injury. Glycogen deposition and content in the hepatic tissue was detected using periodic acid-Schiff (PAS)
staining and a glycogen quantification kit, respectively. Western blotting was performed for semi-quantitative analysis of
protein level and inhibitory phosphorylation of GSK-3, and a Coomassie brilliant blue G-250-based colorimetric assay was
used to detect calpain activity in the liver. Results Glycogen content in the liver decreased significantly after LPS challenge in
all the 3 groups (P<0.05) but showed no significant difference among the groups (P>0.05). Both LPS and lithium chloride
pretreatments caused a significant increase of liver glycogen content (P<0.05). LPS pretreatment induced inhibitory
phosphorylation of GSK-3β (P<0.05) and partial cleavage of GSK-3α but did not affect the expression of GSK-3 protein (P>
0.05). Large-dose LPS challenge significantly increased the activity of calpain in the liver tissue (P<0.05) to a comparable level
in the 3 groups (P>0.05). Conclusion Endotoxin pretreatment induces inhibitory phosphorylation of GSK-3β and partial
cleavage of GSK-3α and promotes the deposition of liver glycogen but does not affect the activity of calpain, which may
contribute to an increased glycogen reserve for energy supply in the event of large-dose LPS challenge.