The Retinal Pigment Epithelium Utilizes Fatty Acids for Ketogenesis
| Autor: | James B. Hurley, Nancy J. Philp, Jianhai Du, Cynthia Moffat, Erin L. Seifert, Jeffrey Adijanto |
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| Rok vydání: | 2014 |
| Předmět: |
Hydroxymethylglutaryl-CoA Synthase
Male Monocarboxylic Acid Transporters genetic structures Citric Acid Cycle Retinal Pigment Epithelium Biology Biochemistry Mice chemistry.chemical_compound Ketogenesis medicine Animals Humans Eye Proteins Molecular Biology Beta oxidation Cells Cultured Retina Retinal pigment epithelium 3-Hydroxybutyric Acid Symporters Fatty acid metabolism Fatty Acids Retinal Cell Biology Photoreceptor outer segment eye diseases Metabolism medicine.anatomical_structure chemistry Saturated fatty acid Female sense organs |
| Zdroj: | Journal of Biological Chemistry. 289:20570-20582 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m114.565457 |
| Popis: | Every day, shortly after light onset, photoreceptor cells shed approximately a tenth of their outer segment. The adjacent retinal pigment epithelial (RPE) cells phagocytize and digest shed photoreceptor outer segment, which provides a rich source of fatty acids that could be utilized as an energy substrate. From a microarray analysis, we found that RPE cells express particularly high levels of the mitochondrial HMG-CoA synthase 2 (Hmgcs2) compared with all other tissues (except the liver and colon), leading to the hypothesis that RPE cells, like hepatocytes, can produce β-hydroxybutyrate (β-HB) from fatty acids. Using primary human fetal RPE (hfRPE) cells cultured on Transwell filters with separate apical and basal chambers, we demonstrate that hfRPE cells can metabolize palmitate, a saturated fatty acid that constitutes .15% of all lipids in the photoreceptor outer segment, to produce β-HB. Importantly, we found that hfRPE cells preferentially release β-HB into the apical chamber and that this process is mediated primarily by monocarboxylate transporter isoform 1 (MCT1). Using a GC-MS analysis of (13)C-labeled metabolites, we showed that retinal cells can take up and metabolize (13)C-labeled β-HB into various TCA cycle intermediates and amino acids. Collectively, our data support a novel mechanism of RPE-retina metabolic coupling in which RPE cells metabolize fatty acids to produce β-HB, which is transported to the retina for use as a metabolic substrate. |
| Databáze: | OpenAIRE |
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