GlaxoSmithKline is currently testing a weight loss pill that brings new hope for the persons with weight problems: the pill activates a protein called PPAR-delta. The pill was created as the result of studies on the effects of enhanced PPAR-delta on mice muscle and metabolism. Initially, the effect of PPAR-delta activation was obtained by modifying genetically the mice. The new drug, called GW501516, activates PPAR-delta directly.

The protein was the subject of scientific analysis performed by professor Ronald M. Evans of the Salk Institute for Biological Studies in La Jolla, Calif. This aspect concerned professor Evans for a long time. A decade ago, Evans discovered that this protein's activation regulates fat metabolism.

Drug action: effects of PPAR-delta increase

Evans' latest study (the results of which were published in August 2004) was performed to show that PPAR-delta had measurable effects in terms of weight change. The study was made on genetically engineered mice to produce extra PPAR-delta in their muscle. The protein modifies the composition of skeletal muscle.

Muscle consists of:

• fast-twitch fibers — which burn sugar and are used for rapid movements;
• slow-twitch fibers — which burn fat and are used for sustained activity.

The protein doubles the amount of the slow-twitch muscle, thus determinig an increase in the fat-burning process and a greater endurance.

So, the pill activating PPAR-delta may open the way for a new class of weight-loss drugs, having the results of sustained physical exercise.

The health benefits

They are quite remarkable:

• obesity cure and prevention;
• cure for disorders related to obesity — diabetes and lipid disorders (cholesterol levels), heart disease etc;
• increase in physical condition by preventing physical fatigue and enhance the quality of exercise.

Study results

Compared to unmodified mice, the results of the study were as follows:

• being put on a high fat, high calorie diet, the transgenic mice gained only a third of the weight gained by the unmodified mice;
• even when kept inactive, the transgenic mice remained resistant to obesity;
• the endurance increased substantially - the mice with increased PPAR-delta could run twice the distance normal mice did, being nicknamed “marathon mice”.

Professor Evans suspected also changes in the cardiovascular and nervous systems.

No serious side effects were noticed from the extra PPAR-delta.

Another experiment was made to compare transgenic mice with mice having been given the drug GW501516. The effects were quite similar, including protection against weight gain.

The pill on tests

The drug is being tested by GlaxoSmithKline in obese and diabetic patients for its effects on disorders of fat metabolism such as high blood cholesterol. Further tests are to be made regarding the way the drug affects endurance and weight.

What is truly valuable in the pill is the fact that it does not attempt changes in appetite, as this is hard to accomplish, appetite being genetically programmed. The functioning principle is increasing metabolism to burn more energy.

A potential problem, acknowledged by Evans, will probably be constituted by abuse among athletes, that could take them to enhance performance, but the benefits resulting from this exceptional work are far too important opening new possibilities in treating metabolic ailments (obesity, derived disease - diabetes, heart disease) that have constanly increased their rate of occurrence lately.