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Record W2988581613 · doi:10.1016/j.jhepr.2019.10.009

Pcsk9 knockout exacerbates diet-induced non-alcoholic steatohepatitis, fibrosis and liver injury in mice

2019· article· en· W2988581613 on OpenAlex
Paul Lebeau, Jae Hyun Byun, Khrystyna Platko, Ali Al‐Hashimi, Šárka Lhoták, Melissa E. MacDonald, Aurora Mejía‐Benítez, Annik Prat, Suleiman A. Igdoura, Bernardo L. Trigatti, Kenneth N. Maclean, Nabil G. Seidah, Richard C. Austin

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueJHEP Reports · 2019
Typearticle
Languageen
FieldMedicine
TopicLiver Disease Diagnosis and Treatment
Canadian institutionsHamilton Health SciencesThrombosis and Atherosclerosis Research InstituteMcMaster UniversityUniversité de MontréalMontreal Clinical Research InstituteSt. Joseph’s Healthcare Hamilton
FundersCanadian Institutes of Health ResearchAmgen CanadaAmgenFondation LeducqMcMaster UniversityCanada Research ChairsHeart and Stroke Foundation of Canada
KeywordsSteatohepatitisSteatosisFatty liverCD36Internal medicineEndocrinologyLiver injuryPCSK9HepatocyteBiologyAlcoholic liver diseaseLDL receptorChemistryLipoproteinMedicineCholesterolBiochemistryReceptorCirrhosis

Abstract

fetched live from OpenAlex

The fatty acid translocase, also known as CD36, is a well-established scavenger receptor for fatty acid (FA) uptake and is abundantly expressed in many metabolically active tissues. In the liver, CD36 is known to contribute to the progression of non-alcoholic fatty liver disease and to the more severe non-alcoholic steatohepatitis, by promoting triglyceride accumulation and subsequent lipid-induced endoplasmic reticulum (ER) stress. Given the recent discovery that the hepatocyte-secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) blocks CD36 expression, we sought to investigate the role of PCSK9 in liver fat accumulation and injury in response to saturated FAs and in a mouse model of diet-induced hepatic steatosis. METHODS: mice. RESULTS: , our findings also highlight CD36 as a strong contributor to steatosis and liver injury in the context of PCSK9 deficiency. CONCLUSIONS: Collectively, our findings demonstrate that PCSK9 regulates hepatic triglyceride content in a manner dependent on CD36. In the presence of excess dietary fats, PCSK9 can also protect against hepatic steatosis and liver injury. LAY SUMMARY: knockout mice develop increased liver injury in response to a high-fat diet.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.758

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.010
GPT teacher head0.253
Teacher spread0.243 · 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