Skip to main content
. 2012 May 1;122(6):2176–2194. doi: 10.1172/JCI41636

Figure 12. Antilipotoxic effect of ChREBP overexpression in mouse liver.

Figure 12

Upon ChREBP overexpression in livers of mice fed a HFD, glycolysis and lipogenesis are stimulated, leading to the development of hepatic steatosis. ChREBP overexpression by stimulating SCD1 activity leads to a modification in lipid composition (namely a change in the monounsaturated [MUFA] to saturated [SFA] ratio) and dissociates hepatic steatosis from insulin resistance. Increased phosphorylation of Akt (Ser473 and Thr308) and of downstream substrates was measured in HFD-fed ChREBP mice, and glucose tolerance was improved. Our results provide insights into the causal relationship between hepatic steatosis and insulin resistance and demonstrate that increasing the lipogenic pathway may protect against insulin resistance by raising beneficial lipid species. CRTC2, CREB-regulated transcription coactivator 2; PPARGC1A, peroxisome proliferator-activated receptor γ coactivator 1-α; PCK1, phosphoenolpyruvate carboxykinase.