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Record W4385694006 · doi:10.1126/sciadv.adf7119

TNIK is a conserved regulator of glucose and lipid metabolism in obesity

2023· article· en· W4385694006 on OpenAlexfundno aff
Tang Cam Phung Pham, Lucile Dollet, Mona Sadek Ali, Steffen H. Raun, Lisbeth L. V. Møller, Abbas Jafari, Nicholas Ditzel, Nicoline R. Andersen, Andreas M. Fritzen, Zachary Gerhart‐Hines, Bente Kiens, Anu Suomalainen, Stephen J. Simpson, Morten Salling Olsen, Arnd Kieser, Peter Schjerling, Anni I. Nieminen, Erik A. Richter, Essi Havula, Lykke Sylow

Bibliographic record

VenueScience Advances · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolism, Diabetes, and Cancer
Canadian institutionsnot available
FundersHelsinki Institute of Life Science, Helsingin YliopistoBispebjerg HospitalDiabetestutkimussäätiöNovo Nordisk FondenOrionin TutkimussäätiöSigrid Juséliuksen SäätiöHospital for Sick ChildrenMaud Kuistilan MuistosäätiöNovo NordiskH. Lundbeck A/SJane ja Aatos Erkon SäätiöSickkids Research InstituteBiocenter FinlandLundbeckfondenDeutsche ForschungsgemeinschaftEuropean Commission
KeywordsEndocrinologyLipid metabolismInternal medicineLipogenesisInsulin resistanceGlucose homeostasisSteatosisBiologyCarbohydrate metabolismType 2 diabetesAdipose tissueInsulinDiabetes mellitusMedicine

Abstract

fetched live from OpenAlex

Obesity and type 2 diabetes (T2D) are growing health challenges with unmet treatment needs. Traf2- and NCK-interacting protein kinase (TNIK) is a recently identified obesity- and T2D-associated gene with unknown functions. We show that TNIK governs lipid and glucose homeostasis in Drosophila and mice. Loss of the Drosophila ortholog of TNIK , misshapen , altered the metabolite profiles and impaired de novo lipogenesis in high sugar–fed larvae. Tnik knockout mice exhibited hyperlocomotor activity and were protected against diet-induced fat expansion, insulin resistance, and hepatic steatosis. The improved lipid profile of Tnik knockout mice was accompanied by enhanced skeletal muscle and adipose tissue insulin-stimulated glucose uptake and glucose and lipid handling. Using the T2D Knowledge Portal and the UK Biobank, we observed associations of TNIK variants with blood glucose, HbA1c, body mass index, body fat percentage, and feeding behavior. These results define an untapped paradigm of TNIK-controlled glucose and lipid metabolism.

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)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
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 head0.010
GPT teacher head0.271
Teacher spread0.261 · 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

Citations30
Published2023
Admission routes1
Has abstractyes

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