University of Maryland Researchers Identify New Fat Hormone That May Play a Role in Development of Type 2 Diabetes

For immediate release: August 16, 2006

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Karen Warmkessel

kwarmkessel@umm.edu | 410-328-8919

Study suggests omentin may enhance the effect of insulin on glucose metabolism in body

University of Maryland researchers have discovered a fat hormone ”“ omentin ”“ that may explain the link between obesity and a person's likelihood of developing Type 2 diabetes. The results of the study, which was funded by the National Institutes of Health, have been published in the American Journal of Physiology: Endocrinology and Metabolism.

An estimated 17 million people in the United States have Type 2 diabetes, a condition in which the body either doesn't produce enough insulin to regulate blood sugar levels or can't properly use the insulin that it makes. Obesity, particularly abdominal obesity, is a major risk factor.

“We found that omentin is produced by the fat tissue that surrounds our internal organs. This research, led by Dr. Da-Wei Gong, suggests that this hormone enhances the effect of insulin on the regulation of sugar within the body and therefore may be a factor in causing abdominal obesity and related diseases, such as Type 2 diabetes,” says Alan R. Shuldiner, M.D., a noted diabetes researcher involved in the study who is head of the Department of Medicine's Division of Endocrinology, Diabetes and Nutrition and director of the Program in Genetics and Genomic Medicine at the University of Maryland School of Medicine.

“We believe this newly discovered hormone may affect energy metabolism and body fat distribution, particularly the fat that accumulates in the abdomen,” he adds.

Da-Wei Gong, M.D., Ph.D., associate professor of medicine at the University of Maryland School of Medicine and the study's senior author, says that additional research is needed to determine exactly the role omentin may play in obesity, insulin resistance and Type 2 diabetes. “Future analysis of omentin's biological actions, and measurement of omentin levels in abdominal fat and in blood from individuals who are obese and those who are not, will help us define the protein's role in the development of diabetes and related diseases,” he says.

Dr. Shuldiner notes that levels of some proteins found in fat tissue, such as leptin, increase with obesity, while other fat proteins, such as adiponectin, decrease.

Omentin is one of a group of adipokines, or signaling proteins produced by fat (adipose) tissue. In addition to leptin and adiponectin, other proteins in this group include resistin and a recently discovered protein called visfarin, which mimics the effect of insulin. Many scientists now view fat tissue as the body's largest hormone-producing organ because of its role in regulating metabolism and other body functions.

There are two types of fat in the human body ”“ subcutaneous fat that lies below the skin, and visceral, or omental fat, that is buried beneath the muscles within the abdomen. Visceral fat has been associated with insulin resistance, Type 2 diabetes, cardiovascular disease and a group of ailments known as “metabolic syndrome” to a greater extent than subcutaneous fat.

“The underlying reason for the difference between these two types of fat and why abdominal fat carries more health risks is not well understood. So we decided to take a closer look at visceral fat, examining it on a molecular level,” Dr. Gong says. “Using highly

sophisticated genetic screening methods, we analyzed more than 10,000 tiny bits of genetic material from human fat tissue and discovered this novel visceral fat-specific protein that we named omentin.”

The hormone was prevalent in visceral fat, but barely detectable in subcutaneous fat tissue, which comprises more than 80 percent of the fat in the body, according to the researchers. They found omentin in blood as well, suggesting that the protein's effect on glucose metabolism may be system-wide.

“We also discovered that the omentin gene is located on a region of a chromosome that has been previously linked to Type 2 diabetes,” Dr. Gong says. Dr. Shuldiner and his colleagues at the University of Maryland who are studying diabetes in the Old Order Amish in Lancaster County, Pa., have connected that region on chromosome 1 to Type 2 diabetes, as have other researchers studying other populations.

Dr. Shuldiner says that the omentin gene may one day prove useful in identifying an individual's susceptibility to Type 2 diabetes and the metabolic syndrome. Omentin or other agents that modulate its activity or levels also have potential as new therapeutic agents.

Other University of Maryland researchers involved in the omentin study include Susan K. Fried, Ph.D., John McLenithan, Ph.D., and Rong-Ze Yang, M.D., Ph.D., of the Division of Endocrinology, Diabetes and Nutrition.

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