How the brain regulates liver function has not been extensively studied. Now, Sun, Zhu and colleagues show that, in mice, neurons from the paraventricular hypothalamic nucleus (PVH) regulate the homeostasis of bile acids in the liver. The gene encoding brain-derived neurotrophic factor (BDNF) undergoes alternative splicing, producing nine Bdnf mRNAs that contain different exons and are differentially expressed across brain regions.
Previous studies suggested that BDNF translated specifically from Bdnf mRNA including exon 1 of the gene (Bdnf-e1 mRNA) might have a role in communication between the brain and the periphery. Here, the authors found that mice lacking this transcript (Bdnf-e1−/− mice) exhibited increases in serum and hepatic cholesterol levels and an overall phenotype that resembled metabolic dysfunction-associated fatty liver disease (MAFLD). This indicates that BDNF translated from transcripts including exon 1 has a role in regulating liver function.
This is a preview of subscription content, access via your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription Receive 12 print issues and online access Prices may be subject to local taxes which are calculated during checkout Sun, M. et al. Brain control of hepatic bile acid homeostasis through Bdnf exon I-positive neurons in the paraventricular hypothalamus. Commun. https://doi.org/10.1038/s41467-026-77334-1 (2026).
Article PubMed PubMed Central Google Scholar Nature Reviews Neuroscience http://www.nature.com/nrn/ Yates, D. Brain regulation of bile acids. Neurosci. (2026). https://doi.org/10.1038/s41583-026-01089-3 DOI: https://doi.org/10.1038/s41583-026-01089-3
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