Blocking β-alanine synthesis reveals widespread metabolic changes in the brain
It is finally out! After following the project from the first experiments to publication, one of Selina’s PhD manuscripts is now published in Molecular Metabolism. The study shows that disrupting β-alanine synthesis leads to widespread, sex-specific changes in brain metabolism.
Published: (Updated: )
In our lab, we recently investigated how disruption of β-alanine synthesis affects brain metabolism. In a new study published in Molecular Metabolism (external link), we focused on the enzyme GADL1, a key contributor to β-alanine production in the brain.
Using a multi-omics approach combining metabolomics, proteomics and transcriptomics, we analysed a GADL1 knockout mouse model to map molecular changes across brain regions. Even modest reductions in β-alanine led to widespread metabolic alterations, highlighting its central role in maintaining cellular homeostasis.
We found pronounced sex-specific differences in the response to β-alanine depletion. Female mice showed broad changes linked to oxidative stress and synaptic remodeling, whereas males displayed more localized alterations, including lipid accumulation and shifts in energy metabolism.
Across brain regions, GADL1 loss disrupted lipid metabolism, mitochondrial function and antioxidant balance. These changes were accompanied by alterations in pathways related to neurotransmission and neuroimmune signaling, linking β-alanine metabolism to key processes relevant for brain function.
Overall, our findings demonstrate that GADL1 and β-alanine are central regulators of brain metabolism, with effects that depend on sex and brain region.