Compound mimics calorie restriction - Biomedicine - peroxisome proliferator activated receptor-delta - Brief Article

Science News, Feb 2, 2002 by D.C.

A chemical agent now under development mimics the health benefits of long-term calorie restriction and may help ward off diseases of aging such as diabetes and heart disease.

Animals whose food intake is restricted to about two-thirds of what they would otherwise consume develop diabetes and heart disease later in life than do animals that eat to their heart's content, says Barbara C. Hansen of Johns Hopkins University in Baltimore (SN: 3/15/97, p. 162). However, such severe calorie restriction isn't a likely way of preventing disease in people.

The new agent mimics a compound called peroxisome proliferator activated receptor-delta, or PPAR-delta. In the body, PPAR-delta and related compounds handle cholesterol and fat and govern cells' sensitivity to insulin (SN: 4/17/01, p. 238).

To see whether the PPAR-delta mimic wards off diseases of aging, Hansen took six middle-aged male monkeys with abnormally high concentrations of fatty acids in their blood. The animals also had abnormally low concentrations of high-density-lipoprotein-linked (HDL) cholesterol, or good cholesterol. In monkeys and people, these conditions increase the risk of heart disease. The monkeys were also less sensitive to insulin than normal, an early sign of diabetes.

After 4 weeks on the PPAR-delta mimic, the monkeys had HDL cholesterol concentrations in their blood that were on average 79 percent higher than when they started. They also had fatty acid concentrations 56 percent below their initial concentrations, and the animals' sensitivity to insulin increased over the course of the study. Moreover, the agent had no apparent side effect, Hansen reported last month at a meeting on metabolic diseases in Tempe, Ariz.

"Especially for HDL, I've never seen a more powerful agent," Hansen says.

Although the study is small, if it holds up in people, "the public health impact could be enormous," says Andrezej Bartke of Southern Illinois University in Carbondale. The new compound is already being tested in people, Hansen says.