No more binge eating: signal pathway in the brain that controls food intake discovered

|

A scientist working on a mass spectrometer.
Yan Li analysing probes using a mass spectrometer. Source: Anna Schroll/Leibniz-HKI

The brain controls our body’s lysophospholipids, which in turn control a programme that activates nutritional intake. Specific inhibitors of lipid synthesis could serve as new obesity therapies. This was shown in a study by the Universities of Cologne, Münster and Yale (USA), in which researchers from the Leibniz-HKI were also involved. The results were published in Nature Metabolism.

The scientists showed that a group of nerve cells in the hypothalamus (so-called AgRP, agouti-related peptide neurons) control the release of endogenous lysophospholipids, which in turn control the excitability of nerve cells in the cerebral cortex, which stimulates food intake.

In this process, the crucial step of the signalling 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. The administration of autotaxin inhibitors can thereby significantly reduce both excessive food intake after fasting and obesity in animal models.

The Transfer Group Anti-infectives of the Leibniz-HKI analysed the metabolism and bioavailability of the autotaxin inhibitors for the study. Robert Nitsch, professor at the Faculty of Medicine at the University of Münster, sees the findings as an important step towards new drug development: "The data show that people with a disturbed synaptic LPA signalling pathway are more likely to be overweight and suffer from type II diabetes. This is a strong indication of a possible therapeutic success of ATX inhibitors, which we are currently developing together with the Hans Knöll Institute in Jena for use in humans."

Original publication

Endle H, Horta G, Stutz B, Muthuraman M, Tegeder I, Schreiber Y, Snodgrass IF, Gurke R, Liu Z-W, Sestan-Pesa M, Radyushkin K, Streu N, Fan W, Baumgart J, Li Y, Kloss F, Groppa S, Opel N, Dannlowski U, Grabe HJ, Zipp F, Rácz B, Horvath TL, Nitsch R, Vogt J (2022). AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids. Nature Metabolism, doi: 10.1038/s42255-022-00589-7

Staff

Florian Kloß
Yan Li