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Bokkyoo Jun, William C Gordon, Nicolas G Bazan; Adiponectin receptor 1 (AdipoR1) is necessary for the synthesis of very long chain polyunsaturated fatty acids (VLC-PUFAs) in Photoreceptor Cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):26.
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The abundance of docosahexaenoic acid (DHA) and VLC-PUFAs is reduced in retinal degenerative diseases. We have found that ablation of AdipoR1 leads to decreased DHA uptake and retention with concomitant photoreceptor degeneration. Stargardt’s, a group of juvenile onset macular degenerative diseases, is most frequently caused by mutations in ABCA4 gene (autosomal recessive). Also mutations in ELOVL4 (Elongation of Very Long Chain polyunsaturated fatty acids) gene (autosomal dominant) are causative. Thus we asked if AdipoR1 ablation in mice is necessary for synthesis of VLC-PUFA.
Lipids were extracted from retinas and retinal pigment epithelial (RPE) cells from AdipoR1 knockout (KO) and control mice, and loaded onto a liquid chromatography-mass spectrometer (LC-MS/MS) for analysis. We analyzed VLC-PUFA abundance (in retina and in retina- free eye caps) including their presence in phosphatidylcholine molecular species (using PC 28:0 as internal standard) after naturally occurring isotopes were corrected using self-made programs.
AdipoR1 KO mice showed VLC-PUFA depletion, ranging from 32 carbons to 38 carbons with 6, 5 or 4 double bonds, from both retina and the RPE. DHA content was selectively reduced while arachidonic acid (20:4) was unchanged. AdipoR1 KO mice also displayed compensatory low abundance very long chain fatty acid-containing phosphatidylcholine species, in which arachidonic acid is substituted for DHA.
AdipoR1 regulates selectively DHA uptake/retention and is necessary for photoreceptor cell function. Upon AdipoR1 ablation, DHA uptake is impaired, photoreceptor-specific VLC-PUFA-containing phosphatidylcholine molecular species are reduced, and photoreceptor integrity is compromised. Therefore AdipoR1 is a key regulator of photoreceptor cell survival through DHA uptake, retention, conservation, and elongation to VLC-PUFAs.
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