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Lack of responsiveness to plant sterols in wild type C57BL/6J mice is due to increased HMG‐CoA reductase transcription and higher fractional cholesterol synthesis rate

2009· article· en· W2810917640 on OpenAlexafffund
Todd C. Rideout, Scott Harding, Peter J.H. Jones

Bibliographic record

VenueThe FASEB Journal · 2009
Typearticle
Languageen
FieldMedicine
TopicCholesterol and Lipid Metabolism
Canadian institutionsUniversity of Manitoba
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsInternal medicineEndocrinologyHMG-CoA reductaseCholesterolReductaseHydroxymethylglutaryl-CoA reductaseChemistryBiologyMedicineBiochemistryEnzyme

Abstract

fetched live from OpenAlex

Although plant sterols (PS) are effective in reducing plasma cholesterol (C) in humans and various animal models, previous work suggests that wild type C57BL/6J mice do not respond to PS therapy despite reductions in intestinal cholesterol absorption. To explain this non‐responsiveness, we examined changes in hepatic HMG‐CoA reductase (HMG‐CoAr) expression and C synthesis in C57BL/6J mice. Mice (n = 10) were fed a high‐fat control diet or the control diet with 2% PS for 30 d in a randomized block design. Mice received an intraperitoneal injection of deuterium oxide 2h prior to sacrifice and whole‐body C synthesis was measured by deuterium incorporation. Although total C and non‐HDL C did not differ between treatments, PS consumption reduced ( P <0.05) plasma triglycerides by 29% compared to control (0.68±0.02 vs. 0.91±0.17 mmol/L). PS consumption increased hepatic HMG‐CoAr mRNA expression (2.7 fold of control, P <0.05) but did not affect ( P >0.05) HMG‐CoAr protein abundance. In agreement with HMG‐CoAr mRNA expression, PS consumption increased whole‐body fractional C synthesis rate compared to control (2.0±0.16 vs. 1.3±0.43 % day −1 ). HMG‐CoAr mRNA expression was positively correlated with whole‐body C synthesis (r = 0.61, P <0.05). The lack of response of plasma C to PS consumption in C57BL/6J mice is due to an upregulation of hepatic HMG‐CoAr mRNA expression and a compensatory increase in C synthesis. Funded by NSERC.

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)0.001
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 score0.011
Threshold uncertainty score0.037

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.001
Science and technology studies0.0010.002
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0020.004
Insufficient payload (model declined to judge)0.0110.003

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 head0.038
GPT teacher head0.293
Teacher spread0.256 · 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

Citations0
Published2009
Admission routes2
Has abstractyes

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