ejrideout.bsky.social
My lab studies sex differences in metabolism and metabolic disease in flies and mice. #sexdifferences #Drosophila #lipid #insulin #betacell
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Congratulations!
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Last week we learnt how basic science research using #Drosophila #genetics is transforming lives via precision medicine for treating rare metabolic disorders from the newly minted PhD - Holly Thorpe.
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Congratulations š Hope you can carve out time to celebrate!
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Sounds like a great initiative, happy to connect š
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Congratulations - what a brilliant story š¤©
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Thank you very much!
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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).
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Iām so sorry š
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While we didn't test other phenotypes, many different adult traits are regulated by IIS. The sex difference in this important pathway may therefore affect other aspects of physiology, lifespan, and reproduction. While this is a brief summary, there's a lot more in the paper - happy reading!
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What's cool is that this suggests males and females maintain their optimal set point of fat storage via two mechanisms: females achieve higher fat storage through higher activity of the anabolic effects of IIS, whereas males have lower stored fat due to higher activity of catabolic pathways.
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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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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.
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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.
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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.
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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.
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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!