Clues to curbing obesity found in neuronal 'sweet spot'

August 1, 2014
Green POMC neurons were activated by leptin (red nuclei). Credit: Yale University

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.

Published in the Aug. 1 issue of The Journal of Clinical Investigation (JCI), the study showed that when the researchers blocked the effects of the PPARgamma in a small number of in mice, the animals ate less and became resistant to a high-fat diet.

"These ate fat and sugar, and did not gain weight, while their control littermates gained weight on the same diet," 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 ."

POMC neurons are found in the hypothalamus and regulate food intake. When activated, these neurons cause a feeling of fullness and curb appetite. PPARgamma regulates the activation of these neurons.

Diano and her team studied 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," said Diano, who is also professor of comparative medicine and neurobiology at Yale and director of the Reproductive Neurosciences Group.

The 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, but patients gain weight on these medications.

"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 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 . Our next step is to test this theory in diabetes mouse models."

Explore further: Improved understanding of appetite-control proteins suggest treatment of obesity

More information: PPARγ ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding, J Clin Invest. doi:10.1172/JCI76220

Related Stories

Recommended for you

Researchers grow retinal nerve cells in the lab

November 30, 2015

Johns Hopkins researchers have developed a method to efficiently turn human stem cells into retinal ganglion cells, the type of nerve cells located within the retina that transmit visual signals from the eye to the brain. ...

Shining light on microbial growth and death inside our guts

November 30, 2015

For the first time, scientists can accurately measure population growth rates of the microbes that live inside mammalian gastrointestinal tracts, according to a new method reported in Nature Communications by a team at the ...

Functional human liver cells grown in the lab

November 26, 2015

In new research appearing in the prestigious journal Nature Biotechnology, an international research team led by The Hebrew University of Jerusalem describes a new technique for growing human hepatocytes in the laboratory. ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.