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 [
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Figure 5Scd1 deficiency normalizes hepatic insulin action in HF-fed mice. (
A) Protocol for Scd1 ASO treatment in mice. Male C57BL/6J mice were allocated to a HF diet for 3 weeks. Five days before the completion of the protocol (day 0), the mice received an i.p. injection of either a SCR ASO or Scd1 ASO (100 mg/kg of body weight); on day 3, the animals received a second ASO injection, and vascular catheters were implanted; finally, on day 5, the mice were subjected to an insulin clamp procedure. (
B) Scd1 ASO (black bars) markedly decreased the hepatic levels of Scd1 mRNA and protein compared with SCR ASO (grey bars) in HF diet–fed mice. (
C) Protocol for the insulin clamp procedure in mice. (
D) The enzymatic (desaturase) activity of Scd1 was markedly increased by HF feeding in mice (gray versus white bars) and dramatically lowered by treatment with Scd1 ASO (black bars). The rapid attenuation of liver Scd1 expression and activity prevented the development of hepatic insulin resistance induced by HF feeding in mice but did not modify insulin action on glucose uptake. *
P < 0.05 versus SCR ASO;
n = 6–10.