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

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.

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Cite

BibTeX RIS

BibTeX

@misc{juber2026method,
  title = {{Method to Identify Liver-to-Brain Region-Specific Crosstalk Using TurboID}},
  author = {M. C. Juber and A. Asghari and K. E. Claflin and M. J. Potthoff},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.03.749208},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749208v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Method to Identify Liver-to-Brain Region-Specific Crosstalk Using TurboID
AU  - M. C. Juber
AU  - A. Asghari
AU  - K. E. Claflin
AU  - M. J. Potthoff
PY  - 2026
DA  - 2026/09/03
PB  - bioRxiv
DO  - 10.64898/2026.09.03.749208
UR  - https://www.biorxiv.org/content/10.64898/2026.09.03.749208v1
AB  - 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.
ER  -