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Record W4402668655 · doi:10.1038/s42255-026-01508-w

Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis

2024· preprint· en· W4402668655 on OpenAlex
Romane Manceau, Danie Majeur, Celena M. Cherian, Colin J. Miller, Lianna W. Wat, Jasper D. Fisher, Audrey Labarre, Serena Hollman, Sébastien Audet, Charlotte F. Chao, Lewis R Depaauw-Holt, Benjamin A. Rogers, Anthony Bosson, Joyce J.Y. Xi, Catrina A.S. Callow, Niyoosha Yoosefi, Niki Shahraki, Yi Han Xia, Alisa Hui, Jared VanderZwaag, Khalil Bouyakdan, Demetra Rodaros, Pavel Kotchetkov, Caroline Daneault, Ghazal Fallahpour, Martine Tétreault, Marie‐Ève Tremblay, Matthieu Ruiz, Baptiste Lacoste, J. Alex Parker, Ciaran Murphy‐Royal, Tao Huan, Stephanie Fulton, Elizabeth J. Rideout, Thierry Alquier

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueNature Metabolism · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicLipid metabolism and biosynthesis
Canadian institutionsCentre Hospitalier de l’Université de MontréalUniversity of VictoriaUniversité de MontréalMontreal Heart InstituteOttawa HospitalUniversity of British Columbia
FundersNational Institute of General Medical SciencesNational Institutes of Health
KeywordsLipid dropletHomeostasisEnergy homeostasisBiologyLipid metabolismEndoplasmic reticulumNeuronCell biologyOrganelleFunction (biology)NeuroscienceBiochemistry

Abstract

fetched live from OpenAlex

ABSTRACT Lipids are essential for neuron development and physiology. Yet, the central hubs that coordinate lipid supply and demand in neurons remain unclear. Here, we combine invertebrate and vertebrate models to establish the presence and functional significance of neuronal lipid droplets (LD) in vivo . We find that LD are normally present in neurons in a non-uniform distribution across the brain, and demonstrate triglyceride metabolism enzymes and lipid droplet-associated proteins control neuronal LD formation through both canonical and recently-discovered pathways. Appropriate LD regulation in neurons has conserved and male-biased effects on whole-body energy homeostasis across flies and mice, specifically neurons that couple environmental cues with energy homeostasis. Mechanistically, LD-derived lipids support neuron function by providing phospholipids to sustain mitochondrial and endoplasmic reticulum homeostasis. Together, our work identifies a conserved role for LD as the organelle that coordinates lipid management in neurons, with implications for our understanding of mechanisms that preserve neuronal lipid homeostasis and function in health and disease. HIGHLIGHTS Lipid droplets (LD) normally form in neurons across species Neuronal LD are regulated by a conserved gene network Neuronal LD regulation plays a conserved and sex-biased role in maintaining energy homeostasis LD regulation supports ER and mitochondrial function in hunger-activated neurons GRAPHICAL ABSTRACT

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.

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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.592
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0020.002
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 head0.006
GPT teacher head0.233
Teacher spread0.227 · 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