EPISODE 44: Fat Talks: How Worms Decide Not to Eat

Welcome to the next episode of the WOrM Podcast 🪱

Today we’re talking about something fundamental — feeding behaviour — but through a lens you might not expect.

Not calories.

Not food availability.

But fat composition.

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🧬 The central idea

In C. elegans, feeding isn’t just about energy — it’s about lipid balance.

Specifically, the ratio of:

• saturated fatty acids (SFAs)

• and monounsaturated fatty acids (MUFAs)

And this balance determines whether worms:

• stay on food

• leave food

• or actively ignore it

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🔬 What’s really being sensed?

This isn’t happening at the surface.

It’s happening at the endoplasmic reticulum (ER) — where lipid composition alters membrane properties and activates the stress sensor IRE-1.

That signal is then translated into behaviour through:

• neuronal serotonin

• AMPK signalling

• and a neuropeptide system

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⚡ A new behavioural state: “food apathy”

One of the most interesting outcomes in this study is a state the authors call food apathy.

Worms:

• leave concentrated food

• roam even when food is present

• and reduce overall intake

This is not starvation.

It’s not avoidance of toxins.

It’s a metabolically driven behavioural shift.

⸻

🧠 The big connection: GLP-1-like signalling

Here’s where it gets very interesting.

The pathway that drives this behaviour — PDF-1 / PDFR-1 — shows structural and functional similarity to:

• GLP-1

• GIP

• glucagon-related signalling

In other words, the same systems now targeted by weight-loss drugs may have deep evolutionary roots in simple organisms like worms.

Even more striking — a peptide derived from this worm pathway shows:

• reduced food intake

• improved insulin sensitivity

in mice.

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🧠 The take-home message

Feeding behaviour is not just about hunger.

It’s about how metabolism is sensed and interpreted.

In this case:

lipids → ER stress → neuronal signalling → behaviour

And the implication is big:

Some of the most important metabolic signalling systems in humans may have started as basic lipid-sensing circuits in simple organisms.

⸻

📄 Paper discussed

Zhu, F.; Castillo-Quan, J. I.; Ogawa, T.; Wu, Z.; Ding, L.; Sura, M.; Watanabe, Y.; Lentsch, H.; Fernández-Cárdenas, L. P.; Dag, U.; Beck-Sickinger, A.; Wang, M. C.; Kahn, C. R.; Blackwell, T. K. (2026)

Fatty acid regulation of feeding in Caenorhabditis elegans reveals the potential ancestral origin of a GLP-1-like multiagonist signaling system

Proceedings of the National Academy of Sciences (PNAS)

DOI: 10.1073/pnas.2530979123

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