RAMPING up fat metabolism doesn鈥檛 just stop weight gain 鈥� it could also prevent type 2 diabetes.
Previous studies had shown that mice engineered to lack an enzyme called acetyl-CoA carboxylase 2 (ACC2) deposited less fat in their tissues, despite eating up to 40 per cent more than normal mice. Because fatty deposits around the liver can lead to insulin resistance and type 2 diabetes, removing ACC2 should also protect mice from diabetes.
There was a catch, however. For years, researchers had thought that burning more fat meant less carbohydrate would be used up. 鈥淭his is the Randle hypothesis,鈥� says James Ntambi at the University of Wisconsin-Madison. 鈥淚n one metabolic pathway you generate intermediates that inhibit the enzymes of the other metabolic pathway.鈥�
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If this was the case, removing ACC2 could cause carbohydrate levels to rise 鈥� leading to excessively high blood sugar, insulin resistance and the onset of type 2 diabetes.
Now, Gerald Shulman of Yale University and Salih Wakil at the Baylor College of Medicine in Houston, Texas, have found that this doesn鈥檛 happen after all. 鈥淭he old concept that fat oxidation lowers glucose oxidation doesn鈥檛 seem to hold in the ACC2 knockout mice,鈥� says Wakil. 鈥淏oth fat and carbohydrate oxidation are increased.鈥� That means the mice are well protected against insulin resistance and type 2 diabetes, he says (Proceedings of the National Academy of Sciences, ).
Since ACC2 is also found in humans, the mouse result could have implications for diabetes research, as well as leading to new drugs to combat obesity.
鈥淭he result could have implications for diabetes research, as well as leading to new drugs to combat obesity鈥�
Ntambi thinks there is still work to be done, though. ACC comes in two forms. While removing ACC2 protects mice from insulin resistance, removing ACC1 is lethal. 鈥淚t鈥檚 important to get an inhibitor for ACC2 alone,鈥� says Ntambi. 鈥淭hat鈥檚 the challenge.鈥�
