First published August 1, 2005 - More info
Effective therapies for the treatment of obesity, a key element of metabolic syndrome, are urgently needed but currently lacking. Stearoyl-CoA desaturase–1 (SCD1) is the rate-limiting enzyme catalyzing the conversion of saturated long-chain fatty acids into monounsaturated fatty acids, which are major components of triglycerides. In the current study, we tested the efficacy of pharmacological inhibition of SCD1 in controlling lipogenesis and body weight in mice. SCD1-specific antisense oligonucleotide inhibitors (ASOs) reduced SCD1 expression, reduced fatty acid synthesis and secretion, and increased fatty acid oxidization in primary mouse hepatocytes. Treatment of mice with SCD1 ASOs resulted in prevention of diet-induced obesity with concomitant reductions in SCD1 expression and the ratio of oleate to stearoyl-CoA in tissues and plasma. These changes correlated with reduced body adiposity, hepatomegaly and steatosis, and postprandial plasma insulin and glucose levels. Furthermore, SCD1 ASOs reduced de novo fatty acid synthesis, decreased expression of lipogenic genes, and increased expression of genes promoting energy expenditure in liver and adipose tissues. Thus, SCD1 inhibition represents a new target for the treatment of obesity and related metabolic disorders.
Guoqiang Jiang, Zhihua Li, Franklin Liu, Kenneth Ellsworth, Qing Dallas-Yang, Margaret Wu, John Ronan, Christine Esau, Cain Murphy, Deborah Szalkowski, Raynald Bergeron, Thomas Doebber, Bei B. Zhang
Original citation: J. Clin. Invest.115:1030–1038 (2005). doi:10.1172/JCI23962
Citation for this erratum: J. Clin. Invest.115:2297 (2005). doi:10.1172/JCI23962E1
During the preparation of the manuscript, the file conversion process led to the introduction of errors in the Methods section. The correct temperatures and procedures are listed below
Measurement of desaturation index. Fatty acid methyl esters were identified with an Agilent 6890 gas chromatograph connected to an HP-5 column (30 m × 0.32 mm × 0.25 μM film thickness) connected to a flame ionization detector set at 250°C. The column and the injector temperature were set to 50°C. The column temperature was increased to 150°C at 4°C/min, increased to 200°C at 3°C/min, held at 200°C for 25 minutes, and then increased to 225°C at 25°C/min and held at 225°C for 10 minutes. Under these conditions, the Δ9-16:1, 16:0, Δ9-18:1, and 18:0 methyl esters eluted at 14.2, 14.8, 19.4, and 20.2 minutes, respectively. The desaturation index was calculated as the ratios of Δ9-16:1/16:0 and Δ9-18:1/18:0.
We regret this error.