New signalling pathway in the liver discovered

Original title: Binge drinking triggers VGLUT3-mediated glutamate secretion and subsequent hepatic inflammation by activating mGluR5/NOX2 in Kupffer cells.

Binge drinking has emerged as a major public health issue as it leads to a condition called “alcohol-related fatty liver” (AFL). In some patients this could even progress into alcohol-related steatohepatitis (ASH), a more sever stage, through mechanisms that remain incompletely understood.

Researchers in South Korea have attempted to investigate this and, in the process, have discovered a surprising communication system in the liver that resembles neurotransmission in the brain. The study, published in Nature Communication, found that chronic alcohol consumption causes liver cells to accumulate the neurotransmitter glutamate in vesicles via the transporter VGLUT3. A subsequent binge-drinking episode triggers glutamate release, activating nearby Kupffer cells (resident microphages located in the liver) through the mGluR5 receptor (metabotropic glutamate receptor 5), a protein in the brain that helps cells communicate. The trigger ultimately drives oxidative stress, inflammation, and liver injury.

The team also identified “pseudosynapses” formed between swollen liver cells and immune cells, allowing glutamate signalling to occur more efficiently. Blocking either mGluR5 or its downstream target NOX2 significantly reduced liver inflammation in mouse models, highlighting potential new therapeutic targets for alcohol-related steatohepatitis (ASH).

For the liver imaging the team utilized a custom-built laser -scanning intravital confocal microscopy system. Among the excitation sources for the multi-color fluorescence imaging they used the Cobolt 488-MLD laser, the Cobolt Jive 561 nm and the Cobolt 640-MLD lasers.