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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Pearsall, Elizabeth A. Cheng, Rui Zhou, Kelu Takahashi, Yusuke Matlock, H. Greg Vadvalkar, Shraddha S. Shin, Younghwa Fredrick, Thomas W. Gantner, Marin L. Meng, Steven Fu, Zhongjie Gong, Yan Kinter, Michael Humphries, Kenneth M. Szweda, Luke I. Smith, Lois E. H. Ma, Jian-xing |
| Abstract | Background Peroxisome proliferator activated receptor-alpha (PPARα) is a ubiquitously expressed nuclear receptor. The role of endogenous PPARα in retinal neuronal homeostasis is unknown. Retinal photoreceptors are the highest energy-consuming cells in the body, requiring abundant energy substrates. PPARα 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 PPARα is essential for the maintenance and survival of retinal neurons, with Pparα -/- mice developing retinal degeneration first detected at 8 weeks of age. Using extracellular flux analysis, we identified that PPARα mediates retinal utilization of lipids as an energy substrate, and that ablation of PPARα ultimately results in retinal bioenergetic deficiency and neurodegeneration. This may be due to PPARα 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 PPARα in retinal neuronal survival and lipid metabolism, and furthermore underscore the importance of fatty acid oxidation in photoreceptor survival. We also suggest PPARα as a putative therapeutic target for age-related macular degeneration, which may be due in part to decreased mitochondrial efficiency and subsequent energetic deficits. |
| Related Links | https://bmcbiol.biomedcentral.com/counter/pdf/10.1186/s12915-017-0451-x.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17417007 |
| DOI | 10.1186/s12915-017-0451-x |
| Journal | BMC Biology |
| Issue Number | 1 |
| Volume Number | 15 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2017-11-28 |
| Access Restriction | Open |
| Subject Keyword | Life Sciences Age-related macular degeneration Retina Neurodegeneration Retinal energy metabolism Mitochondria Lipids Fatty acid oxidation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Ecology, Evolution, Behavior and Systematics Structural Biology Biochemistry, Genetics and Molecular Biology Plant Science Biotechnology Physiology Agricultural and Biological Sciences Cell Biology Developmental Biology |
| Journal Impact Factor | 4.4/2023 |
| 5-Year Journal Impact Factor | 5.4/2023 |
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