Figure 4. Selective attenuation of liver Scd1 expression normalizes hepatic insulin action in OF rats.

(A) Protocol for the intraportal Scd1 ASO treatment (top panel). An indwelling catheter was placed into the portal vein, and 2 days later (day 0), the animals received a first intraportal injection of either SCR ASO or Scd1 ASO (25 mg/kg of body weight). On day 3, the rats 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 (See Figure 2A). (B) Intraportal Scd1 ASO (black bar) decreased liver Scd1 mRNA when compared with SCR ASO (white bar; left panel). Selective attenuation of liver Scd1 (black bar) in OF rats improved hepatic insulin action when compared with SCR ASO (white bar) as shown by a significant decrease in glucose production (GP) (center panel) and a significant increase in insulin’s ability to inhibit GP (right panel). (C–F) To examine whether the decreased expression of SCD1 in adipose tissue is required for the effects of Scd1 ASO on GP, we compared subgroups of OF rats displaying similar decreases in liver SCD1 induced by either i.p. (C and D) or intraportal (E and F) ASO. (C) i.p. Scd1 ASO markedly suppressed Scd1 expression in liver and white fat. (E) Intraportal Scd1 ASO markedly decreased Scd1 expression in the liver but not in adipose tissue. (D and F) The 2 treatment regimens led to similar improvements in hepatic insulin action. *P < 0.05 versus SCR ASO OF; n = 5–6.