Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival

Nature Communications
Dennis S RiceNicolas G Bazan

Abstract

The identification of pathways necessary for photoreceptor and retinal pigment epithelium (RPE) function is critical to uncover therapies for blindness. Here we report the discovery of adiponectin receptor 1 (AdipoR1) as a regulator of these cells' functions. Docosahexaenoic acid (DHA) is avidly retained in photoreceptors, while mechanisms controlling DHA uptake and retention are unknown. Thus, we demonstrate that AdipoR1 ablation results in DHA reduction. In situ hybridization reveals photoreceptor and RPE cell AdipoR1 expression, blunted in AdipoR1(-/-) mice. We also find decreased photoreceptor-specific phosphatidylcholine containing very long-chain polyunsaturated fatty acids and severely attenuated electroretinograms. These changes precede progressive photoreceptor degeneration in AdipoR1(-/-) mice. RPE-rich eyecup cultures from AdipoR1(-/-) reveal impaired DHA uptake. AdipoR1 overexpression in RPE cells enhances DHA uptake, whereas AdipoR1 silencing has the opposite effect. These results establish AdipoR1 as a regulatory switch of DHA uptake, retention, conservation and elongation in photoreceptors and RPE, thus preserving photoreceptor cell integrity.

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Citations

Jun 7, 2015·Cellular and Molecular Neurobiology·Jorgelina M CalandriaNicolas G Bazan
Aug 21, 2016·Cellular and Molecular Life Sciences : CMLS·Thierry Léveillard, José-Alain Sahel
Apr 4, 2017·Molecular Aspects of Medicine·Jessica Wei, Karsten Gronert
Jan 15, 2016·Journal of Lipid Research·Aruna GorusupudiPaul S Bernstein
Jul 24, 2015·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Olga Lorena GermanNora P Rotstein
Nov 29, 2017·EMBO Molecular Medicine·Zhongjie FuLois Eh Smith
Dec 15, 2015·Human Mutation·Mingchu XuRui Chen
Jun 16, 2017·The Journal of Biological Chemistry·Aram Asatryan, Nicolas G Bazan
Sep 27, 2018·Scientific Reports·Valentin M SluchDennis S Rice
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marie-Audrey I KautzmannNicolas G Bazan
Aug 29, 2020·Journal of Cell Science·Tina StormClare E Futter
May 21, 2019·Molecular Nutrition & Food Research·Aruna GorusupudiPaul S Bernstein
Nov 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·Khanh V DoNicolas G Bazan
Mar 27, 2020·Journal of Cellular and Molecular Medicine·Aurélie CubizollePhilippe Brabet
Feb 26, 2020·Journal of Lipid Research·Zhongjie FuLois E H Smith
Sep 20, 2020·Journal of Lipid Research·M Victoria SimonNawajes Mandal
Feb 9, 2021·Journal of Lipid Research·Gyening Kofi YeboahMartin-Paul Agbaga
Feb 9, 2021·Journal of Lipid Research·Fu ZhongjieE H Smith Lois
Feb 9, 2021·Journal of Lipid Research·Simon M VictoriaMandal Nawajes
Apr 4, 2021·International Journal of Molecular Sciences·Małgorzata B RóżanowskaBartosz Różanowski
May 1, 2021·International Journal of Molecular Sciences·Yannick DasMyriam Baes

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Datasets Mentioned

BETA
M12481

Methods Mentioned

BETA
gene trapping
electron microscopy
gene trap
PCR
biopsy
in vitro transcription
light microscopy

Software Mentioned

BioGPS
Fuji

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