Neuronal 'Sweet Spot' in the Brain Could Curb Tide of Obesity by Preventing Weight Gain

As our nation continues to pack on the pounds, scientists are looking for new waves to curb the tide of obesity. Now, they've found that preventing weight gain could be as easy as keeping a nuclear receptor from being activated in a small part of the brain.

POMC neurons are found in the hypothalamus, a region of our brains. These neurons regulate food intake and when activated, make you feel full and curb appetite. PPARgamma, which is a nuclear receptor, regulates the activation of these neurons.

That's why scientists decided to see if interfering with PPARgamma could help curb obesity. The scientists examined transgenic mice that were genetically engineered to delete the PPARgamma receptor from POMC neurons and then fed the mice a high-fat, high-sugar diet.

"When we blocked PPARgamma in these hypothalamic cells, we found an increased level of free radical formation in POMC neurons, and they were more active," said Sabrina Diano, one of the researchers, in a news release. "These animals ate fat and sugar, and did not gain weight while their control littermates did. We showed that the PPARgamma receptor in neurons that produce POMC could control response to a high-fat diet without resulting in obesity."

The findings have important implications for diabetes. Since PPARgamma is a target of thiazolidinedione (TZD), which is a class of drug used to treate type 2 diabetes, more research should be conducted. TZD lower blood-glucose levels, but patients gain weight on these medications.

"Our study suggested 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. "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."

The findings are published in the Journal of Clinical Investigation.