Nerve cells of a mouse brain (green) and the protein PRG-1 (red). A novel treatment that regulates the excitability of networks that control consuming behavior may be a video game changer in the worldwide battle against obesity.
A group 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 School of Medicine, New Haven, USA) has now shown that control of the excitability of neurons in the cerebral cortex by LPA plays an important function in the control of consuming behavior: AgRP nerve cells manage the quantity of lysophosphatidylcholine (LPC) in the blood. Synaptic LPA signals promote particular networks in the brain, therefore leading to increased food consumption.
In the mouse design, after a period of fasting a boost in LPC in the blood led to a boost in stimulating LPA in the brain.
Scientists have actually discovered a brain circuit that manages food consumption. By inhibiting this path, extreme food intake after fasting and weight problems could be considerably lowered.
A group of researchers has developed a totally new method to dealing with eating disorders.
They showed that a group of afferent neuron (so-called AgRP, agouti-related peptide neurons) in the hypothalamus control the release of endogenous lysophospholipids, which in turn manage the excitability of afferent neuron in the cortex, which stimulates food intake.
In this procedure, the essential action of the signaling pathway is managed by autotaxin, an enzyme that is accountable for the production of lysophosphatidic acid (LPA) in the brain as a modulator of network activity. Administering autotaxin inhibitors can consequently substantially lower both excessive food consumption after fasting and obesity in animal models.
The research study article “AgRP neurons manage food intake behavior at cortical synapses through peripherally-derived lysophospholipids” has now been published in the journal Nature Metabolism.
Nerve cells of a mouse brain (green) and the protein PRG-1 (red). If the afferent neuron contain PRG-1, the cells appear in yellow. Credit: Johannes Vogt
Consuming disorders, especially obesity, are among the leading causes of a wide variety of diseases in industrialized societies across the world, specifically cardiovascular diseases with deadly results or lifelong disabilities such as heart attacks, diabetes, or strokes. An unique treatment that regulates the excitability of networks that control eating behavior might be a game changer in the around the world fight versus obesity.
A group 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 School of Medicine, New Haven, USA) has now shown that control of the excitability of nerve cells in the cerebral cortex by LPA plays a vital role in the control of eating behavior: AgRP nerve cells manage the quantity of lysophosphatidylcholine (LPC) in the blood. Synaptic LPA signals promote specific networks in the brain, therefore leading to increased food consumption.
In the mouse model, after a duration of fasting an increase in LPC in the blood led to an increase in stimulating LPA in the brain. These mice showed typical food-seeking habits. Both might be stabilized by administrating autotaxin inhibitors. Obese mice, on the other hand, lost weight when these inhibitors were administered constantly.
Johannes Vogt described: “We saw a considerable decrease in extreme food intake and obesity through gene anomaly and medicinal inhibition of ATX. Our essential findings on the LPA-controlled excitability of the brain, which we have worked on for several years, therefore likewise play a central function for consuming habits.”
Robert Nitsch sees the findings as an important action towards new drug development: “The information reveal that people with a disrupted synaptic LPA signaling pathway are most likely to be overweight and experience type II diabetes. This is a strong indicator of a possible healing success of ATX inhibitors, which we are presently establishing together with the Hans Knöll Institute in Jena for use in people.”
These findings on the excitation control of neuronal networks in eating habits through lysophospholipids and the brand-new restorative possibilities they recommend could in the future contribute not just to dealing with eating conditions, but psychiatric and likewise neurological illnesses.
Referral: “AgRP nerve cells manage feeding behaviour at cortical synapses via peripherally derived lysophospholipids” by Heiko Endle, Guilherme Horta, Bernardo Stutz, Muthuraman Muthuraman, Irmgard Tegeder, Yannick Schreiber, Isabel Faria Snodgrass, Robert Gurke, Zhong-Wu Liu, Matija Sestan-Pesa, Konstantin Radyushkin, Nora Streu, Wei Fan, Jan Baumgart, Yan Li, Florian Kloss, Sergiu Groppa, Nils Opel, Udo Dannlowski, Hans J. Grabe, Frauke Zipp, Bence Rácz, Tamas L. Horvath, Robert Nitsch and Johannes Vogt, 27 June 2022, Nature Metabolism.DOI: 10.1038/ s42255-022-00589-7.