Lack of the enzyme, acetyl CoA carboxylase 2 or ACC2, appears to turn the adipose or fat cells of mice into fat burners, explaining in part why the animals can eat more and weigh less than their normal counterparts, said Baylor College of Medicine researchers.
The report that appears online today in the Proceedings of the National Academy of Sciences.
"We studied the fat cells in these mice bred to lack ACC2," said Dr. Salih Wakil, chair of the BCM department of biochemistry and molecular biology. "We found that the adipose in the mutant mice are now oxidizing fat, hydrolyzing (breaking down using water) fat, and passing it on to the heart and muscle because there is an increase in oxidation of fat in those organs. It also starts oxidizing glucose. In other words, the adipose tissue is becoming a little more oxidative and less involved in the synthesis and storage of fat. We feel this contributes to the status of the animal."
In prior studies, Wakil and his colleagues have demonstrated the effect ACC2 has on mice. Mice bred to lack the enzyme can eat a high fat, high carbohydrate diet without gaining weight, while their normal counterparts become obese and develop type 2 diabetes.
"This adds another tissue or organ that helps out in the process of energy maintenance," said Wakil. "ACC2 is potentially a key enzyme in the regulation of weight, obesity, and related problems."
Wakil and his colleagues studied the oxidation of fatty acid and glucose in cultures of fat cells isolated from both normal and mutant mice that lacked ACC2. When the mice were fed a normal diet, fatty acid oxidation was 80 percent higher in the fat cells of the mice lacking ACC2 when compared to normal mice. When they were fed a high fat, high carbohydrate diet for four to five months, the ACC2-deficient mice had a 25 percent higher rate of fatty acid oxidation and twofold higher rate of glucose oxidation than the normal mice.
Others who participated in the research included Drs. WonKeun Oh, Lutfi Abu-Elheiga, Parichher Kordari, Zeiwei Gu, Tattym Shaikenov, Subrahmanyam S. Chirala. The work was supported in part by by the Clayton Foundation for Research and the National Institutes of Health.