Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis
Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".