Vitellogenin-2 acts downstream of PRY-1/Axin to regulate lipids and lifespan in C. elegans
Bibliographic record
Abstract
Lipid metabolism plays an essential role in the survival and adaptation of animals under variable environmental conditions. Lipids are important macromolecules that store energy, serve as structural components, and function as signaling molecules (Watts and Ristow 2017; Papsdorf and Brunet 2019). Defects in lipid metabolism are linked to various diseases and aging in eukaryotes. Therefore, understanding the regulation of this process is critical to modulating disease progression (Wymann and Schneiter 2008). We have shown earlier that lipid metabolism in C. elegans is regulated by an Axin family member, PRY-1 (Ranawade et al. 2018). While the signaling network of PRY-1 in this process remains to be investigated, Axin family of proteins are known to function in both WNT dependant and independent pathways to regulate various developmental events (Mallick, et al. 2019). Our transcriptomic analysis of both mRNA and miRNA genes revealed that PRY-1 is involved in lipid synthesis by affecting the expression of genes such as fatty acid desaturases (fat-5, fat-6, and fat-7) and vitellogenins (vit-1, vit-2, vit-3, vit-4, vit-5 and vit-6) (Ranawade et al. 2018; Mallick, et al. 2019). Vitellogenins are yolk lipoproteins, similar to mammalian apolipoprotein B, that bind to complex lipids and aid in their transportation from the intestine to the gonad (Kimble and Sharrock 1983; Grant and Hirsh 1999). Moreover, vit-2 has been shown to negatively regulate longevity and such a role of vit-2 depends on autophagy, lysosomal lipases, DAF-16/FOXO and HLH-30/TFEB (Seah et al. 2016). In this study, we report a new, adult-specific role of vit-2 in pry-1-mediated regulation of lipid levels and lifespan. We analyzed the transcript levels of vit genes in day-1 and day-4 adults and found that vit-2 was the only vitellogenin whose expression was significantly upregulated in pry-1 mutants (Figure 1A). This suggested to us that vit-2 is negatively regulated by pry-1 and may be involved in pry-1-mediated adult-specific processes. To investigate this further, we examined whether vit-2 knockdown during adulthood can rescue the lipid and lifespan defect (Mallick, et al. 2020) of pry-1 mutants. This was done using a vit-1 dsRNA that also knocks down vit-2 due to the sequence similarity (Ranawade et al. 2018). The results showed that the knockdown of vit-1/2 during adulthood significantly rescued lipid levels in pry-1(mu38) (almost 2-fold) (Figures 1B and 1C). Similar experiments in wildtype animals showed a modest increase (by 1.2-fold). We also examined the lifespan phenotype following vit-1/2 RNAi and observed a marked rescue of the lifespan defect (Mallick et al. 2020) in pry-1(mu38) (102% increase in mean lifespan). The wildtype animals showed a comparatively lower increase in the mean lifespan (16.6%) (Figures 1F and 1G). Overall, these findings show that vit-2 functions downstream of pry-1 to regulate both lipid levels and lifespan.
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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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
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".