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Inflammation and gut microbiota-induced hepatic lipogenesis drives metabolic syndrome in TLR5 deficient mice (HUM1P.310)

2015· article· en· W4313356839 on OpenAlexaff
Vishal Singh, Benoit Chassaing, Limin Zhang, Beng San Yeoh, Xia Xiao, K.J. Harvatine, James M. Ntambi, Andrew D. Patterson, Andrew T. Gewirtz, Matam Vijay–Kumar

Bibliographic record

VenueThe Journal of Immunology · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGut microbiota and health
Canadian institutionsInstitute of Infection and Immunity
Fundersnot available
KeywordsTLR5Gut floraMetabolic syndromeLipogenesisInflammationBiologyLiver X receptorEndocrinologyFarnesoid X receptorDyslipidemiaLipid metabolismInternal medicineFatty liverImmunologyBiochemistryTLR2Nuclear receptorTLR4MedicineGeneDiabetes mellitus

Abstract

fetched live from OpenAlex

Abstract The gut microbiota plays a key role in host metabolism. Toll-Like Receptor 5 (TLR5), a flagellin receptor, is required for gut microbiota homeostasis. Accordingly, TLR5 deficient (T5KO) mice are prone to develop microbiota-dependent spontaneous colitis and metabolic syndrome. Herein, we investigated whether metabolic syndrome in T5KO mice correlates with hepatic dyslipidemia and inflammation. T5KO mice displayed elevated neutral lipids with substantial enrichment of C18:1 (n9) relative to wild-type littermates. Oleate enrichment of hepatic lipids was microbiota-dependent. Analyzing cecal contents via 1H NMR-based metabolomics revealed that T5KO mice exhibited elevated short chain fatty acids (SCFA) with a concomitant increase in colonic SCFA receptors and hepatic pro-inflammatory genes and lipogenic enzymes including stearoyl-CoA desaturase1 (SCD1). SCFA treatment further aggravated metabolic syndrome in T5KO mice. Interestingly, deletion of hepatic SCD1 not only prevented hepatic neutral lipid oleate enrichment but also ameliorated hepatic inflammation and metabolic syndrome in T5KO mice. Collectively, these results underscore the key role of the gut microbiota-liver axis in the pathogenesis of metabolic diseases.

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 score0.006
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0060.001

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 head0.014
GPT teacher head0.247
Teacher spread0.233 · 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
Published2015
Admission routes1
Has abstractyes

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