New approach to treating eating disorders

During this process, a critical step of the signaling pathway is controlled by the enzyme autotaxin, which is responsible for the production of lysophosphatidic acid (LPA) in the brain as a modulator of network activity. Therefore, the use of autotaxin inhibitors can significantly reduce both post-fasting food excess and obesity in animal models.

The paper ‘AgRP neurons control food acquisition behavior at cortical synapses via peripherally derived lysophospholipids’ has now appeared in Natural metabolism.


Eating disorders and especially obesity are among the most common causes of many diseases in industrialized societies worldwide, especially cardiovascular diseases with permanent disability or fatal consequences such as heart attack, diabetes or stroke.

The Robert Koch Institute reported in 2021 that 67% of men and 53% of women in Germany are overweight. 23 percent of adults are severely overweight (obese). Attempts to influence eating behavior with drugs have so far proved ineffective.

A novel therapy that modulates the arousal of the eating behavior control network will be a decisive step towards controlling this widespread obesity disease.

The team found increased rates of obesity and type II diabetes in people with impaired conjugated LPA signaling.

A team led by Professor Johannes Vogt (Faculty of Medicine, University of Cologne), Professor Robert Nitsch (Faculty of Medicine, University of Münster) and Professor Thomas Horvath (Yale Medical School, New Haven, USA) have now shown that the control of excitability of neurons in the cerebral cortex by LPA plays an essential role in the control of eating behavior: AgRP neurons regulate the amount of lysophosphatidylcholine (LPC) in the blood. Through active transport, LPC reaches the brain, where it is converted by the enzyme autotaxin (ATX) to LPA, which acts at the synapse.

LPA signals at the synapse stimulate specific networks in the brain, which in turn lead to increased food intake.

In a rat model, after a period of fasting, the amount of LPC in the blood increased leading to an increase in excitatory LPA in the brain. These mice show typical foraging behavior. Both can be normalized using autotaxin inhibitors. On the other hand, obese mice lost weight with continuous use of these inhibitors.

Johannes Vogt explains: ‘We have seen significant reductions in food intake and obesity through genetic mutations and pharmacological inhibition of ATX. Our fundamental findings on LPA-controlled euphoria, which we have studied for many years, therefore also play a central role in eating behavior. ‘

Robert Nitsch sees the finding as an important step in the development of new drugs: ‘The data suggest that people with dysregulated synaptic LPA signaling pathways are more likely to be overweight and develop diabetes type II road. This is a strong indication of the potential for successful treatment of an ATX inhibitor, which we are currently developing together with the Hans Knöll Institute in Jena for use in humans. ‘

These findings on the excitatory control of neuronal networks in eating behavior through lysophospholipids and the novel therapeutic possibilities they suggest in the future may contribute not only to the treatment of the disorder. eating, but also neurological and mental diseases.

Source: Eurekalert

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