Critical role of stearoyl-CoA desaturase–1 (SCD1) in the onset of diet-induced hepatic insulin resistance
J. Clin. Invest. Roger Gutiérrez-Juárez, et al. 116:1686 doi:10.1172/JCI26991 [Go to this article.]

Figure 1
Systemic administration of Scd1 ASO downregulates liver Scd1 expression and activity in OF rats. (A) Schematic of Scd1 role in lipid synthesis. CE, cholesteryl esters; PL, phospholipids; WE, wax esters. (B) Protocol for Scd1 ASO delivery (top panel). Rats received an i.p. injection of either a control ASO (SCR ASO) or Scd1 ASO (100 mg/kg of body weight) on day 0; on day 3, the animals were switched to a lard-enriched diet (HF) and received a second injection of ASOs; lastly, on day 5, an insulin clamp procedure was performed. The livers of OF animals treated with Scd1 ASO (black bars) displayed an 80% decrease in Scd1 mRNA and a 50% decrease in both Scd1 activity and C18 desaturation index. OF (gray bars) did not modify any of these parameters when compared with SC rats (white bars). (C) OF caused a decrease in hepatic LCFA CoA levels, which were restored to SC levels by Scd1 ASO treatment (top left panel). Liver Scd1 deficiency in OF animals (black bars) resulted in a 3.5-fold increase in liver TG (top right panel) when compared with SCR ASO OF animals (gray bars). JNK phosphorylation and activity were markedly increased in OF Scd1-deficient animals as compared with OF control animals, while OF (gray bars) did not have any effect when compared with SC animals (white bars). Wet wt, wet weight. *P < 0.05 versus SCR ASO OF.