abstract |
The present invention emphasizes the role of acetyl-CoA carboxylase in regulating fatty acid oxidation and synthesis, glucose metabolism, and energy homeostasis through its product malonyl-CoA. Disclosed are transgenic mice having an inactivating mutation in the endogenous ACC2 gene encoding acetyl-CoA carboxylase 2 isoform of acetyl-CoA carboxylase. Inactivation of acetyl-CoA carboxylase 2 results in mice displaying reduced malonyl-CoA levels in skeletal muscle and heart, unrestricted fatty acid oxidation, and a phenotype of reduced fat accumulation in liver and fat storage cells. Become. As a result, the mice consume more food but have less fat accumulation and are slimmer than wild-type mice on the same restricted diet. These results indicate that inhibition of ACC2 acetyl-CoA carboxylase can be used to regulate fatty acidification and accumulation for weight control purposes. The present invention provides a useful animal model for modulating malonyl-CoA production by ACC2 in regulating fatty acid oxidation of muscle, heart, liver and other tissues. They also identify potential inhibitors used to study the mechanisms of fat metabolism and weight control. |