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Record W3023337720 · doi:10.1101/2020.05.04.075895

PHOSPHO1, a novel skeletal regulator of insulin resistance and obesity

2020· preprint· en· W3023337720 on OpenAlexaff
Karla J. Suchacki, NM Morton, Calvin Vary, Carmen Huesa, MC Yadav, BJ Thomas, Sophie Rajoanah, L. Bünger, D. R. Ball, Martin E. Barrios‐Llerena, AR Guntur, Zohreh Khavandgar, WP Cawthorn, Marine Ferron, Gérard Karsenty, Monzur Murshed, CJ Rosen, VE MacRae, J.L. Millán, Colin Farquharson

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldMedicine
TopicAdipose Tissue and Metabolism
Canadian institutionsMontreal Clinical Research InstituteMcGill University
Fundersnot available
KeywordsEndocrinologyInternal medicineInsulin resistanceAdipose tissueInsulinBiologyOsteocalcinDiabetes mellitusGlucose homeostasisRegulatorHomeostasisChemistryEnzymeMedicineBiochemistryGeneAlkaline phosphatase

Abstract

fetched live from OpenAlex

Abstract The skeleton is recognised as a key endocrine regulator of metabolism. Here we show that mice lacking the bone mineralization enzyme PHOSPHO1 ( Phospho1 -/- ) exhibited improved basal glucose homeostasis and resisted high-fat-diet induced weight gain and diabetes. The metabolic protection in Phospho1 -/- mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated from Phospho1 -/- mice were enriched for genes associated with energy metabolism and diabetes; Phospho1 both directly and indirectly interacted with genes associated with glucose transport and insulin receptor signalling. Canonical thermogenesis via brown adipose tissue did not underlie the metabolic protection observed in adult Phospho1 -/- mice. However, the decreased serum choline levels in Phospho1 -/- mice were normalized by feeding a 2% choline rich diet resulting in a normalization in insulin sensitivity and fat mass. This study identifies PHOSPHO1 as a potential therapeutic target for the treatment of obesity and diabetes.

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 score0.008

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)0.0020.001

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 head0.016
GPT teacher head0.230
Teacher spread0.214 · 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
Published2020
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicAdipose Tissue and Metabolism→French-language works237,207→