Study data showed that reducing levels of the enzyme prolylcarboxypeptidase (PRCP) led to weight loss and a decreased risk of type 2 diabetes in mice.
The research team found that PRCP is located in the hypothalamus and regulates levels of the alpha-melanocyte stimulating hormone (alpha-MSH), which is a peptide known for inhibiting food intake and stimulating energy expenditure.
Researchers found that blocking the PRCP enzyme keeps the alpha-MSH peptides from being degraded, resulting in higher levels of alpha-MSH and decreased appetite.
"Our research provides the first evidence that breaking down molecules in the brain that regulate metabolism is an important component of weight control. Our findings provide a possible new target for the development of drugs to control metabolic disorders such as obesity and type 2 diabetes," said senior author Sabrina Diano, associate professor in the Departments of Obstetrics, Gynecology and Reproductive Sciences, and Neurobiology.
The study was conducted in congenic mice that were naturally lean and later in mice that had PRCP removed. Animals without the PRCP enzyme were leaner and ate less food.
They also had higher levels of alpha-MSH in the hypothalamus compared to control animals.
The mice were put on a diet of 45 percent fat-the equivalent of eating fast food everyday-and even with this high fat diet, they did not gain as much weight as control animals on a regular diet.
The study was published in the August issue of the Journal of Clinical Investigation.