Fig. 6.

Chronic MLN4924 treatment normalizes blood glucose independent of obesity in WD-fed mice. (A) Western blotting using liver lysate from male C57BL/6J mice fed chow or WD for 12 wk. The red arrow indicates neddylated cullin. (B–J) Male C57BL/6J mice were fed Chow or WD for 16 wk. MLN4924 treatment (60 mg/kg, SQ, every other day) was initiated after mice were fed WD for 7 wk as indicated. Control mice were injected with vehicle. After 16 wk of feeding, mice were fasted from 9 AM to 3 PM and euthanized. (B) Body weight. (C) Blood glucose was measured after 6-h fasting at time of euthanasia. (D) Plasma insulin. (E and F) Hepatic protein by Western blotting and densitometry analysis. (G and H) Relative liver mRNA expression. (I) Liver triglyceride content. (J) Plasma alanine aminotransferase (ALT). Results are expressed as mean ± SEM (n = 5 to 8). Two-way ANOVA and Tukey post hoc test were used to calculate the P value.