Method to Identify Liver-to-Brain Region-Specific Crosstalk Using TurboID

Authors

Juber, M. C., Asghari, A., Claflin, K. E., Potthoff, M. J.

Abstract

Endocrine crosstalk between the liver and the brain regulates systemic energy homeostasis. However, this communication has not been comprehensively evaluated because identification of liver-derived proteins, or hepatokines, is difficult to define using bulk serum proteomics alone. To overcome this problem, we applied hepatocyte-restricted endoplasmic-reticulum targeted TurboID (ER-TurboID) in vivo and recovered biotinylated, liver-secretion competent proteins directly from specific brain regions, including the hypothalamus and hindbrain (nucleus of the solitary tract (NTS) and area postrema (AP)). Compared with AAV8-Null transduced controls, TurboID-expressing animals showed 3- to 21-fold enrichment of liver-expressed and predicted liver-secreted proteins among brain regions, with 81 canonical liver-secretome proteins, including multiple carboxylesterase (CES) family members. These results establish a method to identify novel secreted factors from peripheral tissues that can potentially act on specific brain regions.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Sep 2026.

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