Figure 7. PDZ-RhoGEF contributes to the HFD-induced insulin resistance through a S6K1-mediated negative feedback.
(A) Western blot analysis of insulin-mediated PKB/Akt phosphorylation in peripheral tissues: EWAT, liver, and skeletal muscles (EDL and soleus). (B) Phosphorylation status of IRS1 S632/635, S307, JNK1 T183/185, and p70S6K1 T389 in EWATs from HFD-fed WT and PDZ-RhoGEF KO mice. (C) Phosphorylation of p70S6K1 T389 in EWATs from NCD-fed WT and PDZ-RhoGEF KO mice after in vivo insulin stimulation. (D) Differential protein levels of PDZ-RhoGEF in EWAT of NCD- and HFD-fed wild type mice. (E) PDZ-RhoGEF modulates insulin/IGF-1 signaling to impact adipose tissue homeostasis (I) and susceptibility to dietary-induced obesity and T2D (II).
Figure 7—figure supplement 1. EWAT insulin sensitivity determined by IR tyrosine phosphorylation.
After 14-week of HFD, IR from both WT and PDZ-RhoGEF KO EWAT and liver remained sensitive to insulin, determined by IR tyrosine phosphorylation.