[HTML][HTML] Probing the role of stearoyl-CoA desaturase–1 in hepatic insulin resistance

MT Flowers, M Miyazaki, X Liu… - The Journal of clinical …, 2006 - Am Soc Clin Investig
MT Flowers, M Miyazaki, X Liu, JM Ntambi
The Journal of clinical investigation, 2006Am Soc Clin Investig
Abstract Stearoyl-CoA desaturase–1 (SCD1) catalyzes the synthesis of monounsaturated
fatty acids from saturated fatty acids. Mice with a targeted disruption of Scd1 gene locus are
lean and display increased insulin sensitivity. To examine whether Scd1 activity is required
for the development of diet-induced hepatic insulin resistance, we used a sequence-specific
antisense oligodeoxynucleotide (ASO) to lower hepatic Scd1 expression in rats and mice
with diet-induced insulin resistance. Treatment of rats with Scd1 ASO markedly decreased …
Abstract
Stearoyl-CoA desaturase–1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids from saturated fatty acids. Mice with a targeted disruption of Scd1 gene locus are lean and display increased insulin sensitivity. To examine whether Scd1 activity is required for the development of diet-induced hepatic insulin resistance, we used a sequence-specific antisense oligodeoxynucleotide (ASO) to lower hepatic Scd1 expression in rats and mice with diet-induced insulin resistance. Treatment of rats with Scd1 ASO markedly decreased liver Scd1 expression (~ 80%) and total Scd activity (~ 50%) compared with that in rats treated with scrambled ASO (control). Insulin clamp studies revealed severe hepatic insulin resistance in high-fat–fed rats and mice that was completely reversed by 5 days of treatment with Scd1 ASO. The latter treatment decreased glucose production (by~ 75%), gluconeogenesis, and glycogenolysis. Downregulation of Scd1 also led to increased Akt phosphorylation and marked decreases in the expression of glucose-6-phosphatase (Glc-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Thus, Scd1 is required for the onset of diet-induced hepatic insulin resistance.
The Journal of Clinical Investigation