Neuronal 'Sweet Spot' May Hold the Clues To Curbing Obesity
ByPreventing weight gain or obesity could be as simple as keeping a neuronal "sweet spot" in a small part of the brain from being activated, according to a recent study.
Researchers from Yale's School of Medicine found that blocking the effects of the nuclear receptor PPARgamma in a small number of brain cells may result in people eating less and resisting 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."
POMC neurons are found in the hypothalamus and regulate food intake. They are the neurons that when activated make you feel full and curb appetite. PPARgamma regulates the activation of these neurons.
For the study, researchers examined transgenic mice that were genetically engineered to delete the PPARgamma receptor from POMC neurons. They wanted to see if they could prevent the obesity associated with 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," Diano said. "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."
Diano said the next step is to test "this theory in diabetes mouse models."
The findings were recently published in The Journal of Clinical Investigation.