Effects of choline deficiency in mouse photoreceptor cell line 661W
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PROVIDER: PRJNA1066215 | ENA |
REPOSITORIES: ENA
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Project description:Although mutations in human patatin-like phospholipase PNPLA6 are associated with hereditary retinal degenerative diseases, its mechanistic action in the retina is poorly understood. Here, we uncover the molecular mechanism by which PNPLA6 dysfunction disturbs retinal homeostasis and visual function. PNPLA6, by acting as a phospholipase B, regulates choline mobilization from phosphatidylcholine and subsequent choline turnover for phosphatidylcholine regeneration in retinal pigment epithelial (RPE) cells. PNPLA6-driven choline is supplied from RPE cells to adjacent photoreceptor cells to support their survival. Inhibition of this pathway results in abnormal morphology, proliferation, metabolism, and functions of RPE and photoreceptor cells, and mice with retina-specific PNPLA6 deletion exhibit retinitis pigmentosa-like retinal degeneration. Notably, these abnormalities are entirely rescued by choline supplementation. Thus, PNPLA6 plays an essential role in retinal homeostasis by controlling choline availability for phospholipid recycling and provide a framework for the development of a novel ophthalmic drug target for retinal degeneration.
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Project description:To explore the influence of maternal choline intake on placental gene expression, we employed whole genome microarray expression profiling to identify genes that were differentially expressed in placental tissues obtained from women consuming two different doses (480 vs. 930 mg/d) of choline throughout the third trimester of pregnancy. Healthy third trimester (gestational week 26-29) pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6) or 930 (n=6) mg choline/d. Full thickness placental samples were collected at delivery to extract RNA and perform the arrays. Healthy third trimester (gestational week 26-29) pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6) or 930 (n=6) mg choline/d for 12 weeks. Placental samples were obtained at delivery
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Project description:Although mutations in human patatin-like phospholipase PNPLA6 are associated with hereditary retinal degenerative diseases, its mechanistic action in the retina is poorly understood. Here, we uncover the molecular mechanism by which PNPLA6 dysfunction disturbs retinal homeostasis and visual function. PNPLA6, by acting as a phospholipase B, regulates choline mobilization from phosphatidylcholine and subsequent choline turnover for phosphatidylcholine regeneration in retinal pigment epithelial (RPE) cells. PNPLA6-driven choline is supplied from RPE cells to adjacent photoreceptor cells to support their survival. Inhibition of this pathway results in abnormal morphology, proliferation, metabolism, and functions of RPE and photoreceptor cells, and mice with retina-specific PNPLA6 deletion exhibit retinitis pigmentosa-like retinal degeneration. Notably, these abnormalities are entirely rescued by choline supplementation. Thus, PNPLA6 plays an essential role in retinal homeostasis by controlling choline availability for phospholipid recycling and provide a framework for the development of a novel ophthalmic drug target for retinal degeneration.
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2026-03-25 | GSE319635 | GEO
Project description:Liver fibrosis is a critical global health challenge, often leading to severe liver diseases without timely intervention. Choline deficiency has been linked to metabolic dysfunction associated steatohepatitis (MASH) and liver fibrosis, suggesting choline supplementation as a potential therapeutic approach. This study aimed to explore the therapeutic potential of choline supplementation in liver fibrosis resolution and its effects on cholesterol homeostasis using a mouse model with induced liver fibrosis. Our findings reveal that choline supplementation significantly decreases blood lactate dehydrogenase (LDH) and non-high-density lipoprotein cholesterol (non-HDL-C) levels. Transcriptome analysis showed that choline supplementation primarily induces genes related to cholesterol homeostasis, suggesting a significant impact on liver cholesterol synthesis. However, choline supplementation did not significantly alter the expression of fibrosis-related, choline metabolism-related, or epigenetics-related genes. This study provides novel insights into the role of choline in liver health and cholesterol metabolism, potentially informing treatments for liver fibrosis and related conditions.
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