Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy
Abstract Activation of anaplerosis takes away glutamine from the biosynthetic pathways to the energy-producing TCA cycle. Especially, induction of hyperoxia driven anaplerosis in neurovascular tissues such as the retina during early stages of development could deplete biosynthetic precursors from ne...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07394-w |
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| author | Almut Heinken John M. Asara Gopalan Gnanaguru Charandeep Singh |
| author_facet | Almut Heinken John M. Asara Gopalan Gnanaguru Charandeep Singh |
| author_sort | Almut Heinken |
| collection | DOAJ |
| description | Abstract Activation of anaplerosis takes away glutamine from the biosynthetic pathways to the energy-producing TCA cycle. Especially, induction of hyperoxia driven anaplerosis in neurovascular tissues such as the retina during early stages of development could deplete biosynthetic precursors from newly proliferating endothelial cells impeding physiological angiogenesis and leading to vasoobliteration. Using an oxygen-induced retinopathy (OIR) mouse model, we investigated the metabolic differences between OIR-resistant BALB/cByJ and OIR susceptible C57BL/6J strains at system levels to understand the molecular underpinnings that potentially contribute to hyperoxia-induced vascular abnormalities in the neural retina. Our systems level in vivo RNA-seq, proteomics, and lipidomic profiling and ex-vivo retinal explant studies show that the medium-chain fatty acids serves as an alternative source to feed the TCA cycle. Our findings strongly implicate that medium-chain fatty acids could suppress glutamine-fueled anaplerosis and ameliorate hyperoxia-induced vascular abnormalities in conditions such as retinopathy of prematurity. |
| format | Article |
| id | doaj-art-03f9cab995dd4c55aed363335f1f71ae |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-03f9cab995dd4c55aed363335f1f71ae2025-01-12T12:35:54ZengNature PortfolioCommunications Biology2399-36422025-01-018111310.1038/s42003-024-07394-wSystemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathyAlmut Heinken0John M. Asara1Gopalan Gnanaguru2Charandeep Singh3Inserm UMRS 1256 NGERE, University of LorraineDivision of Signal Transduction/Mass Spectrometry Core, Beth Israel Deaconess Medical CenterDepartment of Ophthalmology, Tufts Medical Center, Tufts University School of MedicineDepartment of Ophthalmology, Tufts Medical Center, Tufts University School of MedicineAbstract Activation of anaplerosis takes away glutamine from the biosynthetic pathways to the energy-producing TCA cycle. Especially, induction of hyperoxia driven anaplerosis in neurovascular tissues such as the retina during early stages of development could deplete biosynthetic precursors from newly proliferating endothelial cells impeding physiological angiogenesis and leading to vasoobliteration. Using an oxygen-induced retinopathy (OIR) mouse model, we investigated the metabolic differences between OIR-resistant BALB/cByJ and OIR susceptible C57BL/6J strains at system levels to understand the molecular underpinnings that potentially contribute to hyperoxia-induced vascular abnormalities in the neural retina. Our systems level in vivo RNA-seq, proteomics, and lipidomic profiling and ex-vivo retinal explant studies show that the medium-chain fatty acids serves as an alternative source to feed the TCA cycle. Our findings strongly implicate that medium-chain fatty acids could suppress glutamine-fueled anaplerosis and ameliorate hyperoxia-induced vascular abnormalities in conditions such as retinopathy of prematurity.https://doi.org/10.1038/s42003-024-07394-w |
| spellingShingle | Almut Heinken John M. Asara Gopalan Gnanaguru Charandeep Singh Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy Communications Biology |
| title | Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy |
| title_full | Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy |
| title_fullStr | Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy |
| title_full_unstemmed | Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy |
| title_short | Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy |
| title_sort | systemic regulation of retinal medium chain fatty acid oxidation repletes tca cycle flux in oxygen induced retinopathy |
| url | https://doi.org/10.1038/s42003-024-07394-w |
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