Signaling Path in Brain Prevents Satiety

DALLASScientists have discovered a signaling pathway in the brain that causes the body to ignore the hormonal messages telling the body to stop eating and burn fat, according to a new study published in Cell Metabolism.

Researchers at UT Southwestern Medical Center identified a signaling pathway in the brain sufficient to induce cellular leptin resistance, which blocks satiety. Leptin resistance also causes an increase in belly fat, which has been shown to predispose people to an increased risk of heart disease, diabetes and metabolic syndrome.

Researchers induced leptin resistance in organotypic brain slices from mice, a technique that enabled the researchers to maintain the cellular and anatomical relationships and some of the network connections that normally exist within the brain. When the researchers manipulated the networkknown as cAMP-EPAC pathwaythey found that activating this previously unexplored signaling avenue is enough to induce leptin resistance within hypothalamic neurons, a critical site of leptin action. They also found that when the pathway was blocked, the cells were no longer resistant to leptin.

In the follow-up experiments, which we conducted in mice, we were able to induce leptin resistance simply by infusing activators of this pathway, further supporting our theory that this signaling pathway may contribute to leptin resistance in obesity," said lead author Dr. Makoto Fukuda, instructor of internal medicine at UT Southwestern.