Glutathione supports lipid abundance in vivo

Gloria Asantewaa, Emily T Tuttle, Nathan P Ward, Yun Pyo Kang, Yumi Kim, Madeline E Kavanagh, Nomeda Girnius, Ying Chen, Renae Duncan, Katherine Rodriguez, Dirk Brenner, Isaac S. Harris*

*Corresponding author for this work

Research output: Working paperPreprint


ells 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 of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in 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.
Original languageEnglish
Number of pages2
Publication statusPublished - 11 Feb 2023

Publication series

NamebioRxiv : the preprint server for biology


Dive into the research topics of 'Glutathione supports lipid abundance in vivo'. Together they form a unique fingerprint.

Cite this