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 family members.
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.
S100 calcium-binding protein B (S100B) is conventionally viewed as a marker of astrocytic injury, blood–brain barrier (BBB) disruption, and neurological disorders. Emerging evidence places S100B within the broader brain–gut–liver axis of inflammatory signaling. This review proposes that S100B is a glial-derived integra...
Qi Liu, Ming Yan, Chun-Lei Ji et al.· Frontiers in Immunology· 0 citations
Hepatocytes are the functional cells of the liver, tasked with metabolizing macronutrients, detoxifying and filtering blood, producing bile, supporting the immune system, and storing essential nutrients. Liver abscesses (LA) destroy hepatocytes and trigger an inflammatory response that can cause reduced feed intake,...
Macy T. Lawrence, Joe D. Roder, T. Schwartz et al.· Journal of Animal Science· 0 citations
How the brain senses and responds to early metabolic stress, and why this process fails differently across sexes and regions, remains poorly understood. Here we show that biliverdin reductase A (BVRA) loss is associated with sex- and brain region-specific effects in response to high-fat diet (HFD) feeding, impairing in...
Simona Lanzillotta, V. Sommella, Barbara Zulli et al.· Redox Biology· 0 citations
Bile acids (BAs) are produced in the liver and regulate whole-body cholesterol balance. Whether and how the brain regulates liver function, including BA homeostasis, remains largely unexplored. Here we show that a subpopulation of liver-connected Bdnf-e1-expressing hypothalamic neurons regulates BA metabolism in the li...
Meng-Fei Sun, Hao-Chen Zhu, Shang-Jin Li et al.· Nature Communications· 1 citation
Opioid use disorder (OUD) disrupts hypothalamic stress signaling, yet the molecular state of human paraventricular nucleus (PVN) corticotropin-releasing hormone (CRH) neurons remains poorly defined. Using single-nucleus RNA sequencing of 343,819 human hypothalamic nuclei, we applied complementary human HYPOMAP/MapMyCel...
Lorna Barrall, Phillip Urbanczyk, Bruno Kluwe-Schiavon et al.· bioRxiv· 0 citations
Investigation of metabolic profile alterations and differential regulation of the PPARγ signaling axis in proximal and distal hepatic tissues following E. granulosus infection in sheep elucidated the molecular mechanisms underlying local lipid metabolic reprogramming, providing novel therapeutic targets for metabolic i...
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
