Preventing weight gain, obesity, and ultimately diabetes could be as simple as keeping a nuclear receptor from being activated in a small part of the brain, according to a new study by Yale School of Medicine researchers.
When the researchers blocked the effects of the nuclear receptor PPARgamma in a small number of brain cells in mice, the animals ate less and became resistant to a high-fat diet. Even though the animals are fat and sugar, they didn’t gain weight, while the control rats – those who didn’t have their PPARgamma blocked – did. Therefore, according to Sabrina Diano, professor at Yale School of Medicine, the PPARgamma receptor in neurons that produce POMC could control responses to a high-fat diet without resulting in obesity.
During the study, transgenic mice were genetically engineered to delete the PPARgamma receptor from the POMC neurons. These neurons are found in the hypothalamus and regulate food intake. They are the neurons that when activated make you feel full and curb appetite. Also, the researchers wanted to see if they could prevent the obesity associated with a high-fat, high-sugar diet by studying PPARgamma which regulates the activation of these neurons.
When PPAEgamma is blocked is the hypothalamic cells, an increased level of free radical formation in POMC neurons was observed. These findings also have key implications in diabetes. PPARgamma is a target of thiazolidinedione (TZD), a class of drugs used to treat type 2 diabetes. They lower blood-glucose levels, however, patients gain weight on these medications.
This study means 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.
Want to see where I got some of my information ?
PPARgamma ablation sensitizes proopiomelancocortin neurons to leptin during high-fat feeding, Lihong Long,Chitoku Toda – click here
Yale News, Clues to curbing obesity found in neuronal ‘sweet spot’ – click here