05:31pm Tuesday 22 October 2019

UC Davis researchers discover key protein responsible for fat storage

(SACRAMENTO, Calif.) — 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.

Fu-Tong Liu

Dr. Fu-Ton Liu © UC RegentsThe 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.

Liu, Yang and their colleagues examined fat cells from the knockout and control mice. They also 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 said. “In addition, the percent of body fat and insulin resistance decreased in the knockout mice as compared to normal mice.”

The galectin-12 findings are in part the result of the resources available through UC Davis’ Mouse Biology Program. The program’s director and study co-author Kent Lloyd is leading efforts to expand on-campus resources through a mouse-based research center devoted to studies of the physiology and genetics of obesity, diabetes and cardiovascular health.

The new Mouse Metabolic Phenotyping Center recently received a $3.8 million grant from the National Institutes of Health. The new center will provide scientists worldwide with complete physiologic characterizations of mice that have been genetically altered for metabolic studies. It will be one of only six such centers in the United States, and the only one that can create the mice for researchers.
“Funding for the new center allows us to apply our expertise in mouse biology to specifically address the causes and effects of disease in multiple organ systems that are involved in metabolism, endocrinology, obesity and appetite regulation,” said Lloyd, a professor and associate dean for research at the UC Davis School of Veterinary Medicine, and director of the UC Davis Mouse Biology Program.

Additional UC Davis authors include Peter Havel, professor of veterinary medicine and project scientists Lan Yu, James Graham and Daniel Hsu. Liu is also a faculty member at Taiwan’s Institute of Biomedical Sciences at Academia Sinica.

The study was funded by grants from the Dean’s Office of the UC Davis School of Medicine, the National Institutes of Health (Liu and Havel) and the Harrison Endowed Chair for Diabetes Research Award (Yang).

UC Davis Health System is advancing the health of patients everywhere by providing excellent patient care, conducting groundbreaking research, fostering innovative, interprofessional education, and creating dynamic, productive partnerships with the community. The academic health system includes one of the country’s best medical schools, a 645-bed acute-care teaching hospital, an 800-member physician’s practice group and the new Betty Irene Moore School of Nursing. It is home to a National Cancer Institute-designated cancer center, an international neurodevelopmental institute, a stem cell institute and a comprehensive children’s hospital. Other nationally prominent centers focus on advancing telemedicine, improving vascular care, eliminating health disparities and translating research findings into new treatments for patients. Together, they make UC Davis a hub of innovation that is transforming health for all. For more information, visit healthsystem.ucdavis.edu.

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