# Control of metabolism by hypoxia and starvation and the consequences for the pattern of ecdysone secretion in Manduca sexta

**Authors:** Viviane Callier, Rebekah Pahren, Shu Wu, Victoria Bolling, H. Frederik Nijhout

PMC · DOI: 10.1242/jeb.251263 · The Journal of Experimental Biology · 2026-02-06

## TL;DR

This study explores how oxygen levels and starvation affect metabolism and metamorphosis in Manduca sexta larvae.

## Contribution

The study reveals that hypoxia does not trigger early metamorphosis but instead delays it by affecting metabolism and ecdysone secretion.

## Key findings

- Blocking spiracles reduced growth rate, metabolic rate, and body size at metamorphosis.
- Hypoxia delayed metamorphosis rather than triggering it prematurely.
- Lactate levels increased at the critical weight, indicating a metabolic shift.

## Abstract

When larvae of Manduca sexta pass a critical weight, they initiate an endocrine cascade that leads to molting and metamorphosis. The critical weight coincides with a leveling off of the metabolic rate, and we hypothesize that it is the size at which the metabolic needs of a growing body reach the maximum capacity of the tracheal system to deliver oxygen. We examined two simple predictions about the role of oxygen supply in the regulation of growth: first, that restricting access to oxygen by blocking spiracles should affect growth and metabolism, and second, that placing larvae in a hypoxic atmosphere shortly before they reached the critical weight should prematurely trigger cessation of growth and metamorphosis. When sets of spiracles were blocked, growth rate was reduced, as was the metabolic rate and the body size at metamorphosis. The effect of blocking the posterior-most spiracles was greater than that of blocking the anterior-most ones, suggesting the presence of a required abdominal factor. Contrary to expectations, placing larvae in hypoxia a day before they reached the critical weight delayed the molt significantly, suggesting that hypoxia is not a trigger for the initiation of metamorphosis. Nevertheless, an increase in lactate levels in the second half of the final instar, and the leveling off of metabolic rate, indicate that a metabolic shift occurs at the critical weight. Ecdysone secretion in starved and hypoxic larvae was delayed by about 2 days relative to feeding controls, which explains the delayed timing of the metamorphic molt.

Summary: Hypoxia in Manduca sexta does not induce a premature molt but reduces metabolic rate and delays the secretion of ecdysone. An increase in lactate is a better indicator of oxygen insufficiency than hypoxia inducible factor (HIF) expression.

## Linked entities

- **Species:** Manduca sexta (taxon 7130)

## Full-text entities

- **Diseases:** hypoxic (MESH:D002534), hypoxia (MESH:D000860)
- **Chemicals:** lactate (MESH:D019344), oxygen (MESH:D010100), ecdysone (MESH:D004440)
- **Species:** Manduca sexta (Carolina sphinx, species) [taxon 7130]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12912263/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12912263/full.md

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Source: https://tomesphere.com/paper/PMC12912263