Evidence map›Paper›PMID 42177944›Full record

ArticleMolecular metabolism2026

Blocking β-alanine synthesis triggers widespread perturbations of energy and lipid metabolism in the brain.

Selina Cannon Homaei, Elaheh Mahootchi, Aashish Srivastava, Mahima Sanjay Gomladu, Oda Caspara Krokengen, Anne Baumann, Jan Haavik

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Article in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Selina Cannon HomaeiDepartment of Biomedicine, University of Bergen, Bergen, Norway. Electronic address: Selina.homaei@uib.no.
Elaheh MahootchiDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Aashish SrivastavaGenome Core-Facility, Clinical Laboratory (K2), Haukeland University Hospital, University of Bergen, Bergen, Norway.
Mahima Sanjay GomladuGenome Core-Facility, Clinical Laboratory (K2), Haukeland University Hospital, University of Bergen, Bergen, Norway.
Oda Caspara KrokengenDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Anne BaumannDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Jan HaavikDepartment of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlutamate decarboxylase-like 1 (GADL1) decarboxylates aspartic acid to β-alanine in several mammalian tissues, particularly in the brain and skeletal muscle. β-alanine is a precursor to the antioxidant and osmoregulatory dipeptide carnosine (β-alanyl-l-histidine), as well as pantothenic acid and coenzyme A. Deletion of GADL1 reduces carnosine and anserine levels in multiple tissues, but the consequences for brain metabolism remain unclear. This study aimed to explore sex-specific metabolic and cellular effects of GADL1 and β-alanine depletion in different areas of the brain. METHODS AND

resultsWe conducted a metabolomic screening of seven mouse tissues, followed by a detailed transcriptomic, proteomic, and metabolomic analysis of cerebrum, cerebellum, and olfactory bulb tissues from male and female GADL1 knockout and wild-type mice to explore sex-, age-, and region-specific molecular alterations. Loss of GADL1 induced distinct, sex-dependent metabolic responses across brain regions. Metabolomic data showed increased oxidative stress and possible synaptic remodeling in the cerebrum of mature females, whereas males exhibited massive lipid accumulation in multiple tissues. A similar pattern appeared in the developing olfactory bulb, where both sexes displayed lipid accumulation, but only males showed signs of inflammatory activation and altered energy metabolism, as supported by transcriptomic and proteomic analyses.

conclusionsGADL1 loss and consequent β-alanine depletion trigger widespread metabolic remodeling in brain tissue. Even modest β-alanine reduction leads to region, age, and sex-specific perturbations of energy metabolism and cellular homeostasis. These findings highlight the multifaceted biochemical roles of β-alanine and suggest that its physiological and therapeutic effects may differ by tissue, sex, and developmental stage.

Indexed as

beta-AlanineBrainEnergy MetabolismLipid MetabolismAnimalsCarnosineFemaleMaleMetabolomicsMiceMice, Inbred C57BLMice, KnockoutOxidative StressProteomicsbeta-AlanineCarnosineCarnosineEnergy homeostasisFatty acid synthesisGlutamate decarboxylase-like 1 (GADL1)Multi-omicsβ-alanine metabolism

Identifiers

PMID42177944
PMCPMC13265694

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.