Fig. 6.

Genetic ablation of adiponectin receptor 1 leads to depletion of VLC-PUFAs and its derivatives in retina. A: Dietary DHA, or DHA derived from dietary 18:3n3, is supplied by the liver and taken by the Adiponectin Receptor 1 (AdipoR1), followed by elongation in the inner segment of photoreceptor cell (PRC) by Elongation of Very Long chain fatty acids-4 (ELOVL4) to VLC-PUFA and incorporation into PC molecular species, which contains DHA at sn-2. During daily PRC outer segment renewal, these PC molecular species interact with rhodopsin and, after shedding of the PRC tips and phagocytosis, become part of retinal pigment epithelium (RPE) cells. Uncompensated oxidative stress (UOS) or other disruptors of homeostasis trigger the release of VLC-PUFAs. 32:6n-3 and 34:6n-3 are depicted generating hydroperoxyl forms, and then elovanoid (ELV)-N32 or ELV-N34, respectively. B: The pool size of free 32:6n-3 in retinas of AdipoR1 KO mice (red) is decreased as compared with that in wild type (WT) (blue). Insert (1) shows ELV-N32 in KO (red) and WT (blue); insert (2) shows monohydroxy 32:6n3, the stable derivative of the hydroperoxyl precursor of ELV-N32, in WT (blue) and lack of detectable signal in the KO (red). C: Similarly, the pool size of free 34:6n-3 in retinas of AdipoR1 KO mice (red) is decreased as compared with that in WT (blue). Insert (1) shows ELV-N32 in KO (red) and WT (blue); insert (2) shows mono-hydroxy 34:6n-3, the stable derivative of the hydroperoxyl precursor of ELV-N34, in WT (blue) and lack of detectable signal in the KO (red). D: RPE cells sustain PRC functional integrity (left); right, the ablation of AdipoR1 switches off DHA availability, and PRC degeneration ensues. Reproduced, with permission, from Scientific Reports [190]. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)