Scientists have found a novel signaling channel in the brain that governs food intake, which might lead to better therapies for binge eating — possibly even a medicine that blocks the impulse to binge eat at the neuronal level.
The neurons to begin with in this case are agouti-related peptide (AgRP) neurons. Researchers discovered that AgRPs are found in the hypothalamus, which regulates various metabolic processes, and that when activated, they can cause feelings of hunger.
AgRPs were also connected to a brain enzyme called autotaxin (ATX) in this study, and by suppressing ATX in mice, the researchers were able to regulate food cravings in the animals.
"We saw a significant reduction in excessive food intake and obesity through gene mutation and pharmacological inhibition of ATX," says Johannes Vogt, a professor at the Faculty of Medicine at the University of Cologne in Germany.
The researchers discovered a route through which AgRPs regulate blood levels of the biomolecule lysophosphatidylcholine (LPC). ATX transports LPC molecules to the brain, where they are converted into lysophosphatidic acid (LPA).
LPA is responsible for stimulating neurons in the brain that stimulate the quest for food. The link was identified by studying fasting mice – mice that developed higher levels of LPC – and confirmed by inhibiting ATX, which controls LPA production. Following a treatment of ATX inhibitors, obese mice lost weight.
After previously linking abnormalities in the LPA signaling pathway to obesity and type 2 diabetes in humans, the researchers believe their results in mice will correspond to similar processes and chain reactions in humans.
"Our fundamental findings on the LPA-controlled excitability of the brain, which we have worked on for years, therefore also play a central role for eating behavior," adds Vogt.
Even though the preliminary results of this mouse experiment are intriguing, the study is still in its early stages. The study's authors note that numerous other mechanisms also contribute to the body's need for food.
This current study might provide the groundwork for future efforts to reduce obesity with medications, which have so far mainly failed. Furthermore, the insights gained here might aid in the treatment of a variety of neurological and mental diseases.
For the time being, the team is designing a series of ATX-blocking medications for future testing. With obesity currently being so prevalent and the source of so many various health issues, a therapy like this might make a significant impact.
"This is a strong indication of a possible therapeutic success of ATX inhibitors," says neuroscientist Robert Nitsch of the University of Münster in Germany.
The research has been published in Nature Metabolism.
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