| First Author | Pearsall EA | Year | 2017 |
| Journal | BMC Biol | Volume | 15 |
| Issue | 1 | Pages | 113 |
| PubMed ID | 29183319 | Mgi Jnum | J:280314 |
| Mgi Id | MGI:6368338 | Doi | 10.1186/s12915-017-0451-x |
| Citation | Pearsall EA, et al. (2017) PPARalpha is essential for retinal lipid metabolism and neuronal survival. BMC Biol 15(1):113 |
| abstractText | BACKGROUND: Peroxisome proliferator activated receptor-alpha (PPARalpha) is a ubiquitously expressed nuclear receptor. The role of endogenous PPARalpha in retinal neuronal homeostasis is unknown. Retinal photoreceptors are the highest energy-consuming cells in the body, requiring abundant energy substrates. PPARalpha is a known regulator of lipid metabolism, and we hypothesized that it may regulate lipid use for oxidative phosphorylation in energetically demanding retinal neurons. RESULTS: We found that endogenous PPARalpha is essential for the maintenance and survival of retinal neurons, with Pparalpha (-/-) mice developing retinal degeneration first detected at 8 weeks of age. Using extracellular flux analysis, we identified that PPARalpha mediates retinal utilization of lipids as an energy substrate, and that ablation of PPARalpha ultimately results in retinal bioenergetic deficiency and neurodegeneration. This may be due to PPARalpha regulation of lipid transporters, which facilitate the internalization of fatty acids into cell membranes and mitochondria for oxidation and ATP production. CONCLUSION: We identify an endogenous role for PPARalpha in retinal neuronal survival and lipid metabolism, and furthermore underscore the importance of fatty acid oxidation in photoreceptor survival. We also suggest PPARalpha as a putative therapeutic target for age-related macular degeneration, which may be due in part to decreased mitochondrial efficiency and subsequent energetic deficits. |
