Yale Enzyme Discovery Offers Hope for a Therapy That Reduces Appetite and Ups Energy

Researchers at Yale School of Medicine in New Haven, Connecticut, have found a brain enzyme that, when blocked, curbs appetite and increases energy levels-both crucial factors in controlling and losing weight.

Their results could lead to the development of a drug to counter obesity and type 2 diabetes. In type 2, weight loss and a high energy level, which helps the body metabolize blood sugar, have been a classic combination for controlling the disease.

The enzyme, called prolylcarboxypeptidase (PRCP), regulates chemical alpha-melanocyte stimulating hormone (alpha-MSH), which reduces appetite and increases the body’s energy levels. If PRCP “over-regulates” alpha-MSH, however, the body experiences greater appetite and a lessening of energy output.

The Yale scientists blocked PRCP from working in nondiabetic laboratory mice. The mice, despite being fed a high-fat diet (45 percent of total calories were from fat) that simulated daily fast-food meals, gained less weight than mice that were fed a regular diet. They also maintained high energy levels.

Mice with suppressed PRCP had higher levels of alpha-MSH in their hypothalami. The effects of PRCP blockage considerably reduced their risk of developing type 2, the scientists reported.

The team was led by senior author Sabrina Diano, associate professor in Yale’s departments of obstetrics, gynecology and reproductive sciences, and neurobiology. Its results were reported in the August issue of the Journal of Clinical Investigation.

The Yale findings come on the heels of a recent report from Indiana University that laboratory rodents experienced a dramatic decrease in body weight and fat mass within a week of being injected with a combination of exenatide and glucagon-two already FDA-approved drugs that are staples in diabetes treatment.

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