UC DAVIS (US) — Shutting down a protein that plays a key role in fat storage may lead to better treatments for obesity and diabetes.
A new study, published online in the early edition of the Proceedings of the National Academy of Sciences, shows mice without the ability to make galectin-12 stored 40 percent less body fat and had increased metabolism and decreased insulin resistance.
“This study for the first time demonstrates the importance of a galectin in energy metabolism,” says senior author Fu-Tong Liu, professor and chair of the department of dermatology at the University of California, Davis.
The breakdown and storage of fat in the body are both tightly controlled processes that involve numerous chemical signals, Liu says.
“In this case, galectin-12 seems to be signaling to fat cells that its time to conserve rather than burn energy,” he says. “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. People with advanced diabetes may experience blindness, require limb amputations, or suffer fatal organ failure.
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.
In order to discover potential treatments for type 2 diabetes, Liu and colleagues have been working to understand the chemical signals involved in normal energy metabolism and storage and isolated and cloned the galectin-12 gene 10 years ago.
Since then, 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, they 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,” says associate project scientist Ri-Yao Yang.
Liu, Yang and colleagues examined fat cells from the knockout and control mice, determined percent body fat for each animal, and administered a glucose challenge test to measure insulin resistance.
“When comparing isolated fat cells from normal mice to fat cells from galectin-12 knockout mice, we found that cells from the knockout mice exhibited an increase in fat metabolism and oxygen consumption,” Yang says.
“In addition, the percent of body fat and insulin resistance decreased in the knockout mice as compared to normal mice.”
The study was funded by grants the National Institutes of Health, the Harrison Endowed Chair for Diabetes Research Award, and the Dean’s Office of the UC Davis School of Medicine.
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