MétaCan
Menu
Back to cohort
Record W4220954100 · doi:10.1073/pnas.2113074119

Destabilization of β Cell FIT2 by saturated fatty acids alter lipid droplet numbers and contribute to ER stress and diabetes

2022· article· en· W4220954100 on OpenAlexaff
Xiaofeng Zheng, Qing Wei Calvin Ho, Minni Chua, Olga Stelmashenko, Xin Yi Yeo, Sneha Muralidharan, Federico Torta, Elaine Guo Yan Chew, Michelle Mulan Lian, Jia Nee Foo, Sangyong Jung, Sunny H. Wong, Nguan Soon Tan, Nanwei Tong, Guy A. Rutter, Markus R. Wenk, David L. Silver, Per‐Olof Berggren, Yusuf Ali

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicLipid metabolism and biosynthesis
Canadian institutionsCentre Hospitalier de l’Université de Montréal
FundersWest China Hospital, Sichuan UniversityLee Kong Chian School of Medicine, Nanyang Technological UniversityInstitute of Molecular and Cell BiologyHorizon 2020Innovative Medicines InitiativeNovo Nordisk FondenNational Natural Science Foundation of ChinaVetenskapsrådetAgency for Science, Technology and ResearchNovo NordiskServierKarolinska InstitutetNanyang Technological UniversitySingapore General HospitalSingapore Eye Research InstituteNational Research Foundation SingaporeNational Research FoundationNational University of SingaporeDiabetes Research and Wellness FoundationMinistry of Education - SingaporeEuropean CommissionSichuan UniversityMinistry of Education, IndiaStichting af Jochnick FoundationDirectorate for Biological SciencesImperial College LondonMedical Research CouncilGenome Institute of SingaporeWellcome Trust
KeywordsIntracellularEndoplasmic reticulumUnfolded protein responseBiogenesisInternal medicineEndocrinologyLipotoxicityLipid dropletChemistryDiabetes mellitusSecretionCell biologyBiochemistryBiologyInsulin resistanceMedicine

Abstract

fetched live from OpenAlex

SignificanceWith obesity on the rise, there is a growing appreciation for intracellular lipid droplet (LD) regulation. Here, we show how saturated fatty acids (SFAs) reduce fat storage-inducing transmembrane protein 2 (FIT2)-facilitated, pancreatic β cell LD biogenesis, which in turn induces β cell dysfunction and death, leading to diabetes. This mechanism involves direct acylation of FIT2 cysteine residues, which then marks the FIT2 protein for endoplasmic reticulum (ER)-associated degradation. Loss of β cell FIT2 and LDs reduces insulin secretion, increases intracellular ceramides, stimulates ER stress, and exacerbates diet-induced diabetes in mice. While palmitate and stearate degrade FIT2, unsaturated fatty acids such as palmitoleate and oleate do not, results of which extend to nutrition 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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.009
GPT teacher head0.239
Teacher spread0.230 · 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

Citations51
Published2022
Admission routes1
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicLipid metabolism and biosynthesisFrench-language works237,207