Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 303, Issue -, Pages 1-6Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2019.02.015
Keywords
Glutathione; Glutamate cysteine ligase; Fatty liver disease; Steatosis; Metabolomics
Funding
- United States National Institute of Health (NIH) [K01AA025093, R24AA022057, U01AA021724]
- NATIONAL CANCER INSTITUTE [ZIABC005708] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Glutathione (GSH), the most abundant cellular non-protein thiol, plays a pivotal role in hepatic defense mechanisms against oxidative damage. Despite a strong association between disrupted GSH homeostasis and liver diseases of various etiologies, it was shown that GSH-deficient glutamate-cysteine ligase modifier subunit (Gclm)-null mice are protected against fatty liver development induced by a variety of dietary and environmental insults. The biochemical mechanisms underpinning this protective phenotype have not been clearly defined. The purpose of the current study was to characterize the intrinsic metabolic signature in the livers from GSH deficient Gclm-null mice. Global profiling of hepatic polar metabolites revealed a spectrum of changes in amino acids and metabolites derived from fatty acids, glucose and nucleic acids due to the loss of GCLM. Overall, the observed low GSH-driven metabolic changes represent metabolic adaptations, including elevations in glutamate, aspartate, acetyl-CoA and gluconate, which are beneficial for the maintenance of cellular redox and metabolic homeostasis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available