Scientists have discovered a new signaling pathway in the brain that controls food intake, and it could eventually give us improved treatments for binge eating – perhaps even a drug that turns off the desire to binge eat at the neural level. The particular neurons to start with here are agouti-related peptide (AgRP) neurons. Researchers established that AgRPs are located in the hypothalamus – which regulates numerous metabolic processes – and that they can trigger sensations of hunger when activated. In this research, AgRPs were also linked to an enzyme in the brain called autotaxin (ATX) through a chemical chain of events, and by inhibiting ATX in mice, the researchers were able to control 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 pathway identified by the researchers shows AgRPs controlling levels of the biomolecule lysophosphatidylcholine (LPC) in the blood. LPC molecules are transported to the brain and are turned into lysophosphatidic acid (LPA) through ATX. LPA is responsible for exciting certain neurons in the brain that prompt the search 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. Obese mice lost weight after a course of ATX inhibitors. Having previously linked disruptions in the LPA signaling pathway to obesity and type 2 diabetes in humans, the researchers think their findings in mice are likely to match up with similar processes and chain reactions in people. "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," says Vogt. It's still early for the research, even though the initial results from this experiment on mice are promising. The team behind the study emphasizes that various other pathways also contribute to the body's requirement to get fed. This latest study could prove to be an important foundation in efforts to control obesity through drugs, efforts that have so far largely failed. What's more, the discoveries made here could also help in treating various neurological and psychiatric illnesses. For now, the team is working on developing a series of ATX-blocking drugs for future testing. With obesity now so widespread and the cause of so many different health problems, a treatment like this could make a major difference. "This is a strong indication of a possible therapeutic success of ATX inhibitors," says neuroscientist Robert Nitsch from the University of Münster in Germany. Source
