The way in which the brain sometimes may fail to tell the body that 'it is full' after a hearty meal has been discovered by scientists.
Researchers at UT Southwestern Medical Center have identified a signalling pathway in the brain that's sufficient to induce cellular leptin resistance, a problem that decreases the body's ability to "hear" that it is full and should stop eating.
"Leptin resistance is a significant factor, yet the mechanisms that underlie the problem remain unclear. The fact that this cellular pathway may be involved is a novel observation," said Dr. Joel Elmquist.
Leptin is a hormone released by fat cells that is known to indicate fullness in the brain. But too much of it and the body becomes immune to the hormone.
When that happens, the body "can't hear" the hormonal messages telling it to stop eating and burn fat.
Instead, a person remains hungry, craves sweets and stores more fat instead of burning it.
For the study, the researchers induced leptin resistance in organotypic brain slices from mice.
When the researchers began manipulating the network - known as cAMP-EPAC pathway - they found that activating this signalling 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 signalling pathway may contribute to leptin resistance in obesity," said Dr. Makoto Fukuda.
"These results are potentially interesting and provocative, but the physiological importance remains to be seen. If, however, this pathway is indeed important, it will offer new insights into the mechanisms that high levels of leptin cause in leptin resistance," said Elmquist.
The study will appear in the March issue of Cell Metabolism.