PT  - JOURNAL ARTICLE
AU  - Wang, Wenyue
AU  - Sherry, Tessa
AU  - Cheng, Xinran
AU  - Fan, Qi
AU  - Cornell, Rebecca
AU  - Liu, Jie
AU  - Xiao, Zhicheng
AU  - Pocock, Roger
TI  - An intestinal sphingolipid promotes neuronal health across generations
AID  - 10.1101/2022.07.24.501274
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.07.24.501274
4099  - http://biorxiv.org/content/early/2022/07/24/2022.07.24.501274.short
4100  - http://biorxiv.org/content/early/2022/07/24/2022.07.24.501274.full
AB  - Maternal diet and environment can influence the neuronal health of offspring. Here, we report that diet-induced intestinal sphingolipid biosynthesis reduces adult-onset neurodegeneration intergenerationally in Caenorhabditis elegans. Feeding C. elegans with ursolic acid (UA), a natural plant product, provides neuroprotection by enhancing maternal provisioning of sphingosine-1-phosphate (S1P) - a bioactive sphingolipid. S1P promotes neuronal health across generations by upregulating transcription of the acid ceramidase-1 (asah-1) gene in the intestine. Intergenerational intestine-to-oocyte S1P transfer is essential for promoting neuronal health and is dependent on the lipoprotein yolk receptor RME-2 (Receptor-Mediated Endocytosis-2). Spatially regulating sphingolipid biosynthesis is critical, as inappropriate asah-1 neuronal expression causes developmental axon outgrowth defects. Our results reveal that sphingolipid homeostasis impacts the development and intergenerational health of the nervous system.One-Sentence Summary An intestinal lipid prevents neurodegeneration across generations.Competing Interest StatementThe authors have declared no competing interest.