Discover Key Protein Responsible for Fat Storage

UC Davis Health System researchers have discovered that a protein called galectin-12 plays a key role in fat storage, a finding that could lead to improvements in treating obesity and diabetes. The researchers found that without the ability to make the protein, mice used in their research investigation stored 40 percent less body fat and had increased fat metabolism and decreased insulin resistance.

"This study for the first time demonstrates the importance of a galectin in energy metabolism," said Fu-Tong Liu, distinguished professor and chair of the UC Davis Department of Dermatology, and senior author on the paper.

The findings, published online this week in the early edition of the Proceedings of the National Academy of Sciences, point to galectin-12 as a potential target for the treatment of obesity and diabetes in humans. The breakdown and storage of fat in the body are both tightly controlled processes that involve numerous chemical signals, Liu said.

"In this case, galectin-12 seems to be signaling to fat cells that its time to conserve rather than burn energy," he said. "If we can interrupt that signal, we have a chance at improving fat metabolism and reducing insulin resistance in patients with obesity and type 2 diabetes."

Obesity is the number-one predictor for the development of diabetes, a leading cause of death and disability in the United States. An estimated 24 million Americans have the disease. Between 90 and 95 percent of them have type 2 diabetes, and about 80 percent of people with type 2 diabetes are overweight or obese.

In its early stages, type 2 diabetes is characterized by insulin resistance. The pancreas is producing insulin, but for unknown reasons the body cannot use the insulin effectively. After several years, insulin production decreases, glucose builds up in the blood and the body cannot make efficient use of its main source of fuel. People with advanced diabetes may experience blindness, require limb amputations or suffer fatal organ failure.

In order to discover potential treatments for type 2 diabetes, Liu and his UC Davis colleagues have been working to understand the chemical signals involved in normal energy metabolism and storage. They isolated and cloned the galectin-12 gene 10 years ago. Since then, their studies have shown that the gene is preferentially expressed in fat cells, and that its expression is required for fat-cell differentiation. To enable a focus on specific biological mechanisms associated with galectin-12, the researchers worked with the UC Davis Mouse Biology Program to obtain genetically customized mice that have had individual genes systematically turned off or "knocked out."

"We decided to create the galectin-12 knockout mice to further clarify the function of this protein in animals," said Ri-Yao Yang, associate project scientist...