According to the study, a set of nerve cells in the hypothalamus known as AgRP neurons, which emit endogenous lysophospholipids, regulate the excitability of nerve cells in the cerebral cortex, which in turn promotes appetite.
Autotaxin, an enzyme that produces lysophosphatidic acid (LPA) in the brain as a regulator of network activity, regulates the critical stage in the signalling cascade in this process. Thus, administration of autotaxin inhibitors can considerably lower obesity in animal models as well as excessive food consumption after fasting.
The study’s research article has recently appeared in Nature Metabolism.
In industrialised countries around the world, eating disorders, especially obesity, are among the main causes of a variety of illnesses, particularly cardiovascular ailments including heart attacks, diabetes, and strokes that can have fatal or lifelong consequences. In Germany, there are 67 percent of men and 53 percent of women who are overweight, according to a report from the Robert Koch Institute from 2021. Overweight adults make about 23% of the population (obese).
Medication-induced attempts to change eating habits haven’t been successful to date. In the global fight against obesity, a breakthrough medication that modifies the excitability of networks that regulate eating behaviour could be a game changer.
The researchers found that individuals with defective synaptic LPA signalling had higher rates of obesity and the associated type II diabetes.
Researchers led by Professors Johannes Vogt, Robert Nitsch, and Thomas Horvath have recently established that LPA plays a crucial role in the regulation of eating behaviour by controlling the excitability of neurons in the cerebral cortex. The quantity of lysophosphatidylcholine (LPC) in the blood is controlled by AgRP neurons. Through active transport, LPC travels to the brain where it is changed into LPA, a substance that is active at synapses, by the enzyme autotaxin (ATX). Specific brain networks are stimulated by synaptic LPA signals, which increases appetite.
Johannes Vogt noted that due to gene mutation and pharmacological suppression of ATX, we saw a considerable decrease in calorie intake and obesity. Therefore, our foundational discoveries about the brain’s LPA-controlled excitability, on which we have been working for years, are crucial for understanding eating behaviour.
The data demonstrate that patients with a disrupted synaptic LPA signalling pathway are more likely to be overweight and have type II diabetes, and Robert Nitsch views the findings as a significant step towards the creation of novel drugs. This strongly suggests that ATX inhibitors, which we are presently developing for use in people in collaboration with the Hans Knöll Institute in Jena, may be successful therapeutically.
These discoveries about the lysophospholipid-mediated excitation control of neural networks in eating behaviour and the novel treatment opportunities they propose may one day help treat not only eating disorders but also neurological and mental ailments.
Parvathy Sukumaran 
