March 2005

Synopses: Biotechnology

Continued from page 1

By Monya Baker (edit)

Insulin Version 2.0
Fat secretes hormone that may control diabetes

CONTEXT: Abdominal fat is a dangerous thing. This is not because the fat clings to internal organs (which it does), but because it secretes a suite of hormones that preserve the fat's existence and affect metabolism. The result is an increased risk of a number of maladies, from diabetes to heart disease. In a series of experiments, researchers led by Iichiro Shimomura at Osaka University found yet another hormone made by abdominal, or visceral, fat -- one that, surprisingly, mimics the beneficial effects of insulin.

METHODS AND RESULTS: Using tissue samples taken from two human volunteers, Shimomura's team first identified genes that were active in visceral fat. The researchers tracked one of these genes to a protein known to help immune cells mature. Next, they studied more than a hundred people and found that the more visceral fat they had, the higher their blood levels of the protein. Another experiment observed mice genetically predisposed to obesity; as they got fatter, blood levels of the protein rose. Because the protein comes from visceral fat, the researchers named the protein "visfatin." Mice completely lacking the gene for visfatin died before birth; mice carrying only one functional copy of the gene had elevated glucose levels. Adding visfatin to liver, fat, and muscle cells had the same effect that insulin did; visfatin even lowered glucose levels in insulin-resistant mice. Still more studies indicated that insulin and visfatin bound to different spots on the same protein (the insulin receptor), which, when activated, causes cells to take in glucose. In fact, when the spot where insulin binds to its receptor was mutated such that insulin could not bind, visfatin still could bind, triggering the same response as insulin.

WHY IT MATTERS: Diabetes occurs when the body doesn't make enough insulin or doesn't respond properly to the hormone. The disease afflicts nearly 200 million people worldwide and is the sixth leading cause of death in the United States. This research opens another route to finding diabetes drugs. Either visfatin or molecules that fit visfatin's binding site could help control the disease. Teasing out the natural role of visfatin may yield insights; though greater amounts of fat produce greater amounts of visfatin, these levels are insufficient to counter the ill effects of obesity. Studies that resolve this paradox may show how obesity and its associated diseases could be prevented or treated.

SOURCE: Fukuhara, A., et al. 2005. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426-430.