Investigators from an international consortium of research institutes, including the Johns Hopkins Bloomberg School of Public Health, have identified compounds that mimic the effects of a low calorie diet without changing the amount of essential nutrients.
The researchers believe it may be possible to design drugs that imitate many of the beneficial effects of calorie restriction resulting in the prevention of diseases, such as diabetes, heart disease and cancer, which are more common in people who are overweight. Their findings are published in the current online issue of the Journal of Biological Chemistry.
Co-author Thomas W. Kensler, PhD, a professor of Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health, explained that calorie restriction has intrigued scientists for decades because it increases the life span of almost every species studied. In mammals, calorie restriction suppresses many diseases associated with the obesity epidemic. However, the mechanisms by which calorie restriction suppresses these diseases are not known.
Lead author, J. Christopher Corton, PhD, with ToxicoGenomics in Chapel Hill, N.C., examined the genetic changes that occur during calorie restriction in mice that were fed a diet for one month containing about 35 percent fewer calories than a normal diet. He explained that these genetic changes, which are referred to as a transcript profile, can be used like a bar-code to distinguish a unique profile from other genetic changes that occur in the body. The researchers compared the profile of calorie restriction with the profiles produced by compounds known to have some properties similar to calorie restriction, including the ability to suppress factors that lead to a number of diseases.
The compounds that shared the greatest similarities in the bar codes included those that have activity towards receptors of interest to the pharmaceutical industry. The receptors include those that are targeted by drugs used to treat high cholesterol and triglyceride levels. One of the receptors, called PPARalpha, is a target for drugs that are currently used to treat high cholesterol and triglyceride levels in people at risk for heart disease.