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ACC2 Weight Loss EnzymeAn enzyme discovered by Baylor College of Medicine researchers is critical to the metabolic pathway that governs the body's ability to burn fat and could open a door into new ways to reduce obesity, diabetes and other fat-related human diseases. In an article in the March 30 issue of the journal Science, Dr. Salih Wakil described mice, whose genes were manipulated to make them deficient in the enzyme acetyl-CoA carboxylase 2, or ACC2, as being able to eat as much as 40 percent more than normal mice and weigh 10 to 15 percent less. ACC1 and ACC2 are involved in producing malonyl-CoA, which is key to the formation of fatty acids and to fat burning. Wakil, chairman of Baylor's department of biochemistry and molecular biology, and his colleagues found that there are two pools of malonyl-CoA in the cell. The one in which ACC1 is important is critical to the formation of the long carbon chain component of fatty acids. The other pool associated with ACC2 regulates the transfer of fatty acids to the mitochondria, the cell's powerhouse. Without AAC2, fat burns continuously in the mitochondria.
Studies demonstrated that the ACC2-deficient mice had nearly one-half the fat of the normal mice. The fatty livers of normal mice looked pale compared to the bright red, virtually fat-free livers of the genetically engineered animals. In one study, the researchers gave the ACC2-deficient mice insulin, which is produced in response to eating carbohydrates. In a normal system, insulin stimulates production of an enzyme that activates ACC1 and ACC2, increasing the production of fatty acids and inhibiting the burning of fat. However, in the ACC2-deficient mouse, "fat oxidation continues in the presence of insulin," Wakil said. "This enzyme ACC2 could be a target for generating drugs that could regulate the burning of fat," Wakil said. "It could be important in the regulation of obesity, treatment of diabetes and eventually even the utilization and accumulation of fat, which could affect diseases such as atherosclerosis." Source: Baylor College of Medicine - Press Release 2001 Articles About Weight Loss Drugs |
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