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An intestinal sphingolipid confers intergenerational neuroprotection
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An intestinal sphingolipid confers intergenerational neuroprotection
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Journal Article
An intestinal sphingolipid confers intergenerational neuroprotection
2023
Overview
In animals, maternal diet and environment can influence the health of offspring. Whether and how maternal dietary choice impacts the nervous system across multiple generations is not well understood. Here we show that feeding
Caenorhabditis elegans
with ursolic acid, a natural plant product, improves axon transport and reduces adult-onset axon fragility intergenerationally. Ursolic acid provides neuroprotection by enhancing maternal provisioning of sphingosine-1-phosphate, a bioactive sphingolipid. Intestine-to-oocyte sphingosine-1-phosphate transfer is required for intergenerational neuroprotection and is dependent on the RME-2 lipoprotein yolk receptor. Sphingosine-1-phosphate acts intergenerationally by upregulating the transcription of the acid ceramidase-1 (
asah-1
) gene in the intestine. Spatial regulation of sphingolipid metabolism is critical, as inappropriate
asah-1
expression in neurons causes developmental axon outgrowth defects. Our results show that sphingolipid homeostasis impacts the development and intergenerational health of the nervous system. The ability of specific lipid metabolites to act as messengers between generations may have broad implications for dietary choice during reproduction.
Wang et al. show that intestinal sphingosine-1-phosphate is transferred to oocytes and influences sphingolipid metabolism in the next generations. In the offspring, sphingosine-1-phosphate protects
Caenorhabditis elegans
neurons against axon fragility.
