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Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.

Brankatschk M, Dunst S, Nemetschke L, Eaton S - Elife (2014)

Bottom Line: This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin.LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation.This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, Cell and Developmental Biology, Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.

ABSTRACT
The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

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LTP enrichments on DRNs are reversible.Panel shows numbers (see also Figure 1—figure supplement 3A,A′,C) of LTP positive neurons/brain hemisphere (red) and Repo positive glia/brain (blue), and DRNs/brain (light grey) or LTP positive DRNs/brain (dark grey) from larvae reared on YF, PF, larva reared on PF till late 2nd instar and transferred on YF and larva reared till late 2nd instar on YF and transferred on PF. p-values (Students t’test) are indicated, superscript numbers = standard deviation.DOI:http://dx.doi.org/10.7554/eLife.02862.018
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fig3s2: LTP enrichments on DRNs are reversible.Panel shows numbers (see also Figure 1—figure supplement 3A,A′,C) of LTP positive neurons/brain hemisphere (red) and Repo positive glia/brain (blue), and DRNs/brain (light grey) or LTP positive DRNs/brain (dark grey) from larvae reared on YF, PF, larva reared on PF till late 2nd instar and transferred on YF and larva reared till late 2nd instar on YF and transferred on PF. p-values (Students t’test) are indicated, superscript numbers = standard deviation.DOI:http://dx.doi.org/10.7554/eLife.02862.018

Mentions: We wondered whether lipids in general were required for LTP accumulation on DRNs. Interestingly however, experiments with plant food (PF) suggest that bulk lipid is not sufficient. PF contains no yeast and is based entirely on plant materials. It has the same caloric content as YF, and slightly more lipid with a different fatty acid composition (Carvalho et al., 2012, see ‘Materials and methods’). Surprisingly, LTP is found only occasionally on DRNs in larvae transferred from YF to PF. Depletion of LTP on DRNs occurs within 16 hr of transfer and is reversible in the same time frame (Figure 3F–F″ and Figure 4A,A′,C and Figure 3—figure supplement 2). Strikingly, despite the abundant calories derived from carbohydrates, proteins and lipids, feeding with PF specifically slows the larval growth phase without lengthening embryonic or pupal development. PF also dramatically extends adult lifespan compared to YF (Figure 4E–G). This suggests that systemic IIS is reduced when larvae are fed with PF, compared to YF. Indeed, FOXO is predominantly nuclear in PF-reared larvae (Figure 3D,D′).10.7554/eLife.02862.019Figure 4.Yeast food promotes fast larval development but reduces average life span.


Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.

Brankatschk M, Dunst S, Nemetschke L, Eaton S - Elife (2014)

LTP enrichments on DRNs are reversible.Panel shows numbers (see also Figure 1—figure supplement 3A,A′,C) of LTP positive neurons/brain hemisphere (red) and Repo positive glia/brain (blue), and DRNs/brain (light grey) or LTP positive DRNs/brain (dark grey) from larvae reared on YF, PF, larva reared on PF till late 2nd instar and transferred on YF and larva reared till late 2nd instar on YF and transferred on PF. p-values (Students t’test) are indicated, superscript numbers = standard deviation.DOI:http://dx.doi.org/10.7554/eLife.02862.018
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4210815&req=5

fig3s2: LTP enrichments on DRNs are reversible.Panel shows numbers (see also Figure 1—figure supplement 3A,A′,C) of LTP positive neurons/brain hemisphere (red) and Repo positive glia/brain (blue), and DRNs/brain (light grey) or LTP positive DRNs/brain (dark grey) from larvae reared on YF, PF, larva reared on PF till late 2nd instar and transferred on YF and larva reared till late 2nd instar on YF and transferred on PF. p-values (Students t’test) are indicated, superscript numbers = standard deviation.DOI:http://dx.doi.org/10.7554/eLife.02862.018
Mentions: We wondered whether lipids in general were required for LTP accumulation on DRNs. Interestingly however, experiments with plant food (PF) suggest that bulk lipid is not sufficient. PF contains no yeast and is based entirely on plant materials. It has the same caloric content as YF, and slightly more lipid with a different fatty acid composition (Carvalho et al., 2012, see ‘Materials and methods’). Surprisingly, LTP is found only occasionally on DRNs in larvae transferred from YF to PF. Depletion of LTP on DRNs occurs within 16 hr of transfer and is reversible in the same time frame (Figure 3F–F″ and Figure 4A,A′,C and Figure 3—figure supplement 2). Strikingly, despite the abundant calories derived from carbohydrates, proteins and lipids, feeding with PF specifically slows the larval growth phase without lengthening embryonic or pupal development. PF also dramatically extends adult lifespan compared to YF (Figure 4E–G). This suggests that systemic IIS is reduced when larvae are fed with PF, compared to YF. Indeed, FOXO is predominantly nuclear in PF-reared larvae (Figure 3D,D′).10.7554/eLife.02862.019Figure 4.Yeast food promotes fast larval development but reduces average life span.

Bottom Line: This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin.LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation.This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, Cell and Developmental Biology, Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.

ABSTRACT
The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

Show MeSH