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Record W4302016072 · doi:10.1101/2022.10.02.510555

Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in obesity

2022· preprint· en· W4302016072 on OpenAlexaff
Liam G. Hall, Juliane K. Czeczor, Timothy Connor, Javier Botella, Kirstie A. De Jong, Mark C. Renton, Amanda J. Genders, Kylie Venardos, Sheree D. Martin, Simon T. Bond, Kathryn Aston‐Mourney, Kirsten F. Howlett, James A. Campbell, Greg R. Collier, Ken Walder, Matthew McKenzie, Mark Ziemann, Sean L. McGee

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsUniversity of British Columbia
FundersMedical Research CouncilDeakin UniversityNational Health and Medical Research CouncilDiabetes Australia
KeywordsInternal medicineEndocrinologyCardiac function curveAdipose tissueObesityDiabetes mellitusMedicineDiseaseHeart failureType 2 diabetesAmyloid betaHomeostasis

Abstract

fetched live from OpenAlex

ABSTRACT There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. While some common aetiological mechanisms are known, the role of amyloid beta 42 (Aβ 42 ) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ 42 , which is increased from adipose tissue of obese mice and is associated with higher plasma Aβ 42 . Increasing circulating Aβ 42 levels in non-obese mice had no effect on systemic glucose homeostasis but had obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. These effects on cardiac function were not observed when circulating levels of the closely related Aβ 40 isoform were increased. Administration of an Aβ neutralising antibody prevented obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ neutralising antibody administration in established obesity prevented further deterioration of cardiac function. Multi-contrast transcriptomic analyses revealed that Aβ 42 impacted pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ 42 inhibited mitochondrial function. These data reveal a role for systemic Aβ 42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.

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 score0.002
Threshold uncertainty score0.007

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.015
GPT teacher head0.249
Teacher spread0.234 · 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
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicAlzheimer's disease research and treatments→French-language works237,207→