So proud of this preprint! The main paper from Puja Biswas @pujabiswas.bsky.social PhD revealing a female-biased role for the insulin/insulin-like growth factor signaling pathway (IIS) pathway in regulating body fat in fruit flies www.biorxiv.org/content/10.1... - ThreadSky

ejrideout.bsky.social • 31 days ago

So proud of this preprint! The main paper from Puja Biswas @pujabiswas.bsky.social PhD revealing a female-biased role for the insulin/insulin-like growth factor signaling pathway (IIS) pathway in regulating body fat in fruit flies https://www.biorxiv.org/content/10.1101/2024.11.18.623936v2

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rcthayer.bsky.social•31 days ago

Nice! 👍 I've been curious about why female flies have an extra fat body around the reproductive tract glands-- do you have a sense how much of these sex differences are because all abdominal fat has sex differences, versus because of any distinct properties of the female reproductive-associated fat?

ejrideout.bsky.social•31 days ago

Great point! While the fat near the female gonad may contribute, we showed in the past that female carcasses with no ovaries still had more fat than males. Also, sugar-dependent change to lipidome only reflects shifts in abdominal carcass (no ovary).

sreeparnap.bsky.social•31 days ago

Very cool story! Looking forward to reading the preprint. Congratulations!

ejrideout.bsky.social•31 days ago

Thank you very much!

ejrideout.bsky.social•31 days ago

Normally, female flies have more body fat than males. Over the past few years we have shown that the reason males have lower fat storage is that they have greater activity of genes and pathways that break down fat. But these mechanisms don't affect fat storage in females. Puja wanted to know why!

ejrideout.bsky.social•31 days ago

Puja figured out that the key dietary nutrient that helped females achieve higher fat storage than males was sugar. Amazing lipidomic/metabolomic experiments done in collaboration with Dr Tao Huan at UBC showed dietary sugar had a female-biased effect on lipid synthesis and triglyceride storage.

ejrideout.bsky.social•31 days ago

Because IIS is a key sugar-responsive pathway, Puja compared IIS regulation between males and females. She found that females have higher mRNA and protein levels of Drosophila insulin-like peptide 3 (dilp3) and greater peripheral insulin sensitivity than males, leading to higher IIS activity in fat.

ejrideout.bsky.social•31 days ago

We were fortunate to collaborate with Dr Mike Gordon @flytaste.bsky.social and Dr Molly Stanley @mollystanley3.bsky.social to show that despite the sex-biased regulation of dilp3 mRNA/protein, the activity of the insulin-producing cells was similar between the sexes across multiple conditions.

ejrideout.bsky.social•31 days ago

This suggested a simple model: dietary sugar intake by females promotes higher dilp3 mRNA/protein, which augments IIS activity to promote fat storage. We confirmed this model by showing adult-specific ablation of the insulin-producing cells caused a female-biased reduction in body fat.

ejrideout.bsky.social•31 days ago

Importantly, overexpression of Dilp3 was sufficient to block the decrease in body fat we normally observe when females are kept on a diet without sugar. This reveals Dilp3 and IIS as key determinants of great fat storage in female fruit flies.

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