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Can burning excess fat be as easy as exhaling? That’s the finding of a provocative new study by researchers at the University of California, Los Angeles (UCLA), who transplanted a fat-burning pathway used by bacteria and plants into mice. The genetic alterations enabled the animals to convert fat into carbon dioxide and remain lean while eating the equivalent of a fast-food diet.

The feat, detailed in the current issue of Cell Metabolism introduces a new approach to combating the growing obesity problem in humans. Although the proof-of-concept study is far from being tested in humans, it may point to new strategies for borrowing biological functions from bacteria and other species to improve human health.

To create the fat-burning mice, the researchers focused on a metabolic strategy used by some bacteria and plants called the glyoxylate shunt. James Liao, a biomolecular-engineering professor at UCLA and a senior author of the study, says, “This pathway is essential for the cell to convert fat to sugar” and is used when sugar is not readily available or to convert the fat stored in plant seeds into usable energy. Liao also says that it’s not known why mammals lack this particular strategy, although it may be because our bodies are designed to store fat rather than burn it.

The glyoxylate shunt is composed of just two enzymes. The researchers first introduced genes for these enzymes from E. coli bacteria into cultured human cells and found that they increased the metabolism of fats in the cells. But surprisingly, rather than converting the fat into sugar as bacteria do, the cells burned the fat completely into carbon dioxide. The scientists analyzed gene expression in the cells and found that the new pathway promoted cellular responses that led the cells to metabolize fats rather than sugar.

The researchers then introduced the genes into the livers of mice. While normal mice gain weight when put on a high-fat diet, Liao says that the engineered mice “remained skinny despite the fact that they ate about the same and produced the same waste” and were as active as their normal counterparts. They also had lower fat levels in the liver and lower cholesterol levels. As in the cultured cells, the engineered mice did not convert the fat into sugar, which could have the dangerous side effect of promoting high blood sugar and diabetes. Instead, the scientists found a measured increase in their carbon dioxide output; the excess fat was literally released into thin air. The mice exhibited no visible side effects, although more detailed studies are necessary to verify that.

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Credit: Jason Dean, University of California, Los Angeles

Tagged: Biomedicine, bacteria, obesity, diet, metabolic engineering, metabolism

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