In the setting of positive energy balance, carbohydrates can be converted to fatty acids through the process of de novo lipogenesis. De novo fatty acid biosynthesis occurs in essentially all cells, but adipose tissue and liver are the major sites with liver thought to be quantitatively more important than fat. The flow of carbons from glucose to fatty acids requires a coordinated series of enzymatic reactions. Citrate produced by the tricarboxylic acid cycle in mitochondria is converted by ATP-citrate lyase (ACL) to acetyl-CoA, which is converted to malonyl-CoA by acetyl CoA carboxylase (ACC). ACC exists as ACC1, a cytosolic isoform important in liver and fat for de novo lipogenesis, and ACC2, a mitochondria-associated isoform with highest expression in muscle tissues. Antisense knockdown of ACC isoforms improves insulin sensitivity and fatty liver