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Record W4322422798 · doi:10.1016/j.celrep.2023.112155

Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress

2023· article· en· W4322422798 on OpenAlexafffund
Travis R. Madaris, Manigandan Venkatesan, Soumya Maity, Miriam C. Stein, Neelanjan Vishnu, Mridula K. Venkateswaran, James G. Davis, R. Karthik, Sukanthathulse Uthayabalan, Cristel Allen, Ayodeji Osidele, Kristen Stanley, Nicholas P. Bigham, Terry M. Bakewell, Melanie Narkunan, Amy Le, Varsha Karanam, Kang Li, Aum Mhapankar, Luke Norton, J. Alexander Ross, Mohammed Aslam, William Reeves, Brij B. Singh, Jeffrey L. Caplan, Justin J. Wilson, Peter B. Stathopulos, Joseph A. Baur, Muniswamy Madesh

Bibliographic record

VenueCell Reports · 2023
Typearticle
Languageen
FieldNursing
TopicMagnesium in Health and Disease
Canadian institutionsWestern University
FundersDivision of ChemistryNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of General Medical SciencesNational Science FoundationCanadian Institutes of Health ResearchCongressionally Directed Medical Research ProgramsNational Institute on AgingDiabetes Research CenterUniversity of PennsylvaniaPfizerNational Heart, Lung, and Blood InstituteU.S. Department of DefenseOhio Cancer ResearchNatural Sciences and Engineering Research Council of CanadaNational Institutes of Health
KeywordsLimitingMitochondrionEndogenyStress (linguistics)ChemistryCell biologyBiologyBiochemistryEngineering

Abstract

fetched live from OpenAlex

The most abundant cellular divalent cations, Mg 2+ (mM) and Ca 2+ (nM-μM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but the physiological significance of this competition remains elusive. In mice consuming a Western diet, genetic ablation of the mitochondrial Mg 2+ channel Mrs2 prevents weight gain, enhances mitochondrial activity, decreases fat accumulation in the liver, and causes prominent browning of white adipose. Mrs2 deficiency restrains citrate efflux from the mitochondria, making it unavailable to support de novo lipogenesis. As citrate is an endogenous Mg 2+ chelator, this may represent an adaptive response to a perceived deficit of the cation. Transcriptional profiling of liver and white adipose reveals higher expression of genes involved in glycolysis, β-oxidation, thermogenesis, and HIF-1α-targets, in Mrs2 −/− mice that are further enhanced under Western-diet-associated metabolic stress. Thus, lowering m Mg 2+ promotes metabolism and dampens diet-induced obesity and metabolic syndrome.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.390
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.031
GPT teacher head0.291
Teacher spread0.259 · 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 teacher head, not a consensus.

Study designObservational
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

Citations28
Published2023
Admission routes2
Has abstractyes

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