Blocking Receptor in Brain can Help Prevent Obesity: Yale Researchers

The researchers at the Yale School of Medicine have identified a "switch in brain" that can help reduce weight gain, obesity and even diabetes.

According to the team, blocking the activity of nuclear receptor PPARgamma in brain cells helped mice become resistant to the effects of high-fat diets.

"These animals ate fat and sugar, and did not gain weight, while their control littermates did," said lead author Sabrina Diano, professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine. "We showed that the PPARgamma receptor in neurons that produce POMC could control responses to a high-fat diet without resulting in obesity."

About a third of all adults living in the U.S are overweight or obese, according to data from the CDC. Obesity is a serious medical condition that leads to several chronic health complications such as heart disease and even cancer.

The research conducted at Yale shows that it might be possible to control and even prevent obesity by just switching off activity of a neuron receptor, at least in mice.

The National Institutes of Health funded the study and it is published in the Journal of Clinical Investigation (JCI).

POMC neurons are located in the hypothalamus. These neurons help reduce apettite and make a person feel full after a meal. PPARgamma regulates the activity of these neurons.

For the study, researchers used mice models that lacked PPARgamma in some brain cells. The team then put these mice on a high-fat, high-sugar diet to see if the genetic tweaking affected their health.

The researchers found that inhibition of PPARgamma in the hypothalamus cells led to an increase in free radical formation in POMC neurons, which in turn led to the rise in the activity of these neurons.

The study even explains why people on some diabetes type-2 medications tend to gain weight. The researchers say that thiazolidinedione (TZD), a class of drugs for diabetes target PARgamma. These drugs lower blood-glucose levels, but lead to weight gain.

"Our study suggests that the increased weight gain in diabetic patients treated with TZD could be due to the effect of this drug in the brain, therefore, targeting peripheral PPARgamma to treat type 2 diabetes should be done by developing TZD compounds that can't penetrate the brain," said Diano in a news release. "We could keep the benefits of TZD without the side-effects of weight gain. Our next steps in this research are to test this theory in diabetes mouse models."