THURSDAY, July 12, 2007 (HealthDay News) -- A protein in blood points to rising amounts of a particularly lethal form of body fat around organs, scientists say.
As levels of retinol-binding protein 4 (RBP4) rise, so do levels of "inter-abdominal fat" linked to an increased risk for heart disease and type 2 diabetes, the researchers say.
"Increased inter-abdominal fat is known to be associated with cardiovascular risk," said study co-author Dr. Barbara B. Kahn, chief of the Division of Endocrinology, Diabetes and Metabolism at Beth Israel Deaconess Medical Center, in Boston.
Reporting in the July issue of Cell Metabolism, her team noted that increased "deep belly" fat around organs has long been linked to an increased risk for insulin resistance and type 2 diabetes. "The regulation of this protein may tell us completely new information about what really causes type 2 diabetes," said Kahn, who is also a professor of medicine at Harvard Medical School.
In the study, the researchers found that the amount of RBP4 in the blood accurately reflected the amount of fat surrounding the abdominal organs. That means that "RBP4 might be able to be used as a marker to indicate cardiovascular risk," Kahn said.
She stressed that RBP4 is not a cause of obesity. However, increased levels appear be associated with this particular type of abdominal-fat obesity.
In the study, Kahn and colleagues looked at biopsy samples of abdominal fat from 196 people. They found that more RBP4 is made in visceral (deep belly) fat compared with the subcutaneous fat that lies just beneath the skin. In addition, blood levels of RBP4 are greater in people who are obese. These people have double or triple the amount of RBP4 compared with normal-weight people.
"The gene expression of RBP4 is increased more in visceral adipose [fat] tissue -- the adipose tissue surrounding the internal organs -- than it is in the subcutaneous adipose tissue," Kahn said. So, levels of RBP4 are higher in people who have a so-called "visceral pattern" of obesity compared with people that have a subcutaneous pattern of obesity, she said.
In earlier research, Kahn's team also found that the levels of RBP4 were elevated in people with insulin resistance, people who are obese, and people with type 2 diabetes. This was also the case in healthy people with a family history of diabetes.
According to Kahn, there's ongoing research into drugs that could lower RBP4 levels.
But there's another tried-and-true means of lowering RBP4, she added.
"Levels can also be regulated by physical exercise," Kahn said. In prior research, her team showed that "people who benefited from an exercise program lowered their levels of serum RBP4 when they got more insulin-sensitive," she said.
Kahn had also shown in earlier research that teens who went on a low-carbohydrate diet along with an exercise program lowered their RBP4 levels.
One expert thinks that lowering RBP4 levels might help treat heart disease and type 2 diabetes.
"This study suggests that RBP4 can be a good biomarker to quantify visceral adiposity, which is closely linked to metabolic syndrome," said Dr. Tae-Hwa Chun, from the Department of Internal Medicine, Metabolism, Endocrinology and Diabetes at the University of Michigan. "This article also supports the notion that all the fats are not equal in their functions."
In experiments with mice, RBP4 decreases insulin sensitivity of muscle and liver tissue, which is considered a precursor to diabetes, Chun said.
"It is still not clear whether RBP4 regulates insulin sensitivity by controlling retinoic acid metabolism or by directly acting on muscle or liver cells," Chun said. "The drug Fenretinide, which is shown to lower RBP4 levels, has been already used as a chemotherapeutic agent for cancer. The side effects of the drug, however, need to be carefully weighed against its possible benefit for metabolic diseases."
In another report published in the same issue of the journal, a research team led by Bruce Spiegelman of the Dana-Farber Cancer Institute in Boston identified a gene called PRDM16 that regulates the production of so-called "brown fat" in mice. Brown fat is a type of fat that actually generates heat and counters obesity caused by overeating.
"Brown fat is present in mice and in human infants, where it keeps them warm by dissipating food energy as heat, instead of storing it as 'white' fat," Spiegelman said in a prepared statement. "Human adults don't have much brown fat, but there is some, and from a therapeutic perspective, the question is whether that pathway can be reactivated."
The researchers hope their discovery will lead to new ways of treating obesity in humans.
For more information on risks for heart disease, visit the American Heart Association.