AI Article Synopsis
- - Cells depend on antioxidants like glutathione (GSH) for survival, with GSH being the most abundant antioxidant regulated by the enzyme GCLC.
- - A study involving the deletion of GSH in adult animals revealed its crucial role in maintaining lipid levels, particularly in the liver, which is key for lipid production.
- - The absence of GSH led to decreased expression of lipogenic enzymes, lower triglyceride levels, and reduced fat stores, highlighting GSH's role in balancing oxidative stress and lipid production through the repression of the transcription factor NRF2.
Article Abstract
Cells 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 models to induce deletion in adult animals. We find that GSH is essential to lipid abundance . 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934595 | PMC |
| http://dx.doi.org/10.1101/2023.02.10.524960 | DOI Listing |
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