| Autor: |
Gloria Asantewaa, Emily T. Tuttle, Nathan P. Ward, Yun Pyo Kang, Yumi Kim, Madeline E. Kavanagh, Nomeda Girnius, Ying Chen, Renae Duncan, Katherine Rodriguez, Fabio Hecht, Marco Zocchi, Leonid Smorodintsev-Schiller, TashJaé Q. Scales, Kira Taylor, Fatemeh Alimohammadi, Zachary R Sechrist, Diana Agostini-Vulaj, Xenia L. Schafer, Hayley Chang, Zachary Smith, Thomas N. O’Connor, Sarah Whelan, Laura M. Selfors, Jett Crowdis, G. Kenneth Gray, Roderick T. Bronson, Dirk Brenner, Alessandro Rufini, Robert T. Dirksen, Aram F. Hezel, Aaron R. Huber, Josh Munger, Benjamin F. Cravatt, Vasilis Vasiliou, Calvin L Cole, Gina M. DeNicola, Isaac S. Harris |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
bioRxiv |
| Popis: |
SUMMARYCells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we developed a series ofin vivomodels to induceGclcdeletion in adult animals. We find that GSH is essential to lipid abundancein vivo. GSH levels are reported to be highest in liver tissue, which is also a hub for lipid production. While the loss of GSH did not cause liver failure, it decreased lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we found that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver’s balance of redox buffering and triglyceride production. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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