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.

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Osmotin is a stable protein that is resistant to heat, acidity and enzymes, meaning it could circulate through the body without being broken down by digestion, he said.

Whether osmotin plays any role in the health benefits attributed to diets high in fruits and vegetables is a tantalizing possibility, and this research opens the door to that question, Bressan said.

"We know that osmotin is an active protein in many of the plants we eat," he said. "We control and label nutrients like fats, carbohydrates and protein - but the really active materials in the foods we eat are the ones we know the least about and don't label in our foods."

Both adiponectin and osmotin jump-start a process called "AMP kinase phosphorylation," which increases both sugar and fat use by muscle cells.

"By binding to the adiponectin receptor, osmotin, like adiponectin, can control the energy status of muscle cells, " said Meena Narsimhan, research scientist at Purdue's Bindley Bioscience Center and a study co-author.

Curiously, adiponectin also can kill some types of mammalian cells, Narsimhan said.

"Other research has shown a strong correlation between low levels of adiponectin and increased risk of breast cancer," she said.

Whether osmotin also has a similarly lethal effect on any types of mammalian cells remains to be seen; however, osmotin, when bound to its receptor on yeast cells, does kill those cells, Narsimhan said.

"What's interesting about this research is that is raises so many questions," she said.

Collaborating researchers in this study include Maria A. Coca, who first isolated the yeast receptor gene, at the Instituto de Biologia Molecular, Barcelona, Spain; Dae-Jin Yun of the Environmental Biotechnology National Core Research Center at Gyeongsang National University, Korea; Jingo Jin, Barbara Damsz and Paul Hasegawa at Purdue's Center for Plant Environmental Stress Physiology; Toshimasa Yamauchi, Yusuke Ito and Takashi Kadowaki at the University of Tokyo Graduate School of Medicine and CREST, Japan Society and Technology Corporation; Jose Pardo with the Instituto de Recuersos Naturales y Agrobioloia in Seville, Spain; and Kyeong Kyu Kim with the Sungkyunkwan University School of Medicine, Suwon, Korea.

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