MétaCan
Menu
Back to cohort
Record W3160757640 · doi:10.1016/j.isci.2021.102457

Cholesterol-binding translocator protein TSPO regulates steatosis and bile acid synthesis in nonalcoholic fatty liver disease

2021· article· en· W3160757640 on OpenAlexafffund
Yuchang Li, Liting Chen, Lu Li, Chantal M. Sottas, Stephanie Petrillo, Anthoula Lazaris, Peter Metrakos, Hangyu Wu, Yuji Ishida, Takeshi Saito, Lucy Golden‐Mason, Hugo R. Rosen, Jeremy J. Wolff, Cristina I. Silvescu, Samuel Garza, Garett Cheung, Tiffany Huang, Jinjiang Fan, Martine Culty, Bangyan L. Stiles, Kinji Asahina, Vassilios Papadopoulos

Bibliographic record

VenueiScience · 2021
Typearticle
Languageen
FieldMedicine
TopicLiver Disease Diagnosis and Treatment
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesUniversity of Southern CaliforniaCanadian Institutes of Health ResearchNational Institute of Allergy and Infectious DiseasesSchool of Pharmacy, University of Southern CaliforniaNational Institutes of HealthNational Institute on Alcohol Abuse and Alcoholism
KeywordsTranslocator proteinNonalcoholic fatty liver diseaseFarnesoid X receptorSteatosisChemistryEndoplasmic reticulumDownregulation and upregulationEndocrinologyUnfolded protein responseBiologyInternal medicineBiochemistryFatty liverMedicineNuclear receptorTranscription factorInflammation

Abstract

fetched live from OpenAlex

Translocator protein (TSPO, 18 kDa) levels increase in parallel with the evolution of simple steatosis (SS) to nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD). However, TSPO function in SS and NASH is unknown. Loss of TSPO in hepatocytes in vitro downregulated acetyl-CoA acetyltransferase 2 and increased free cholesterol (FC). FC accumulation induced endoplasmic reticulum stress via IRE1A and protein kinase RNA-like ER kinase/ATF4/CCAAT-enhancer-binding protein homologous protein pathways and autophagy. TSPO deficiency activated cellular adaptive antioxidant protection; this adaptation was lost upon excessive FC accumulation. A TSPO ligand 19-Atriol blocked cholesterol binding and recapitulated many of the alterations seen in TSPO-deficient cells. These data suggest that TSPO deficiency accelerated the progression of SS. In NASH, however, loss of TSPO ameliorated liver fibrosis through downregulation of bile acid synthesis by reducing CYP7A1 and CYP27A1 levels and increasing farnesoid X receptor expression. These studies indicate a dynamic and complex role for TSPO in the evolution of NAFLD.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.021
GPT teacher head0.257
Teacher spread0.236 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations34
Published2021
Admission routes2
Has abstractyes

Explore more

Same venueiScienceSame topicLiver Disease Diagnosis and TreatmentFrench-language works237,207