Your browser doesn't support javascript.
loading
Glutathione supports lipid abundance in vivo.
Asantewaa, Gloria; Tuttle, Emily T; Ward, Nathan P; Kang, Yun Pyo; Kim, Yumi; Kavanagh, Madeline E; Girnius, Nomeda; Chen, Ying; Duncan, Renae; Rodriguez, Katherine; Hecht, Fabio; Zocchi, Marco; Smorodintsev-Schiller, Leonid; Scales, TashJaé Q; Taylor, Kira; Alimohammadi, Fatemeh; Sechrist, Zachary R; Agostini-Vulaj, Diana; Schafer, Xenia L; Chang, Hayley; Smith, Zachary; O'Connor, Thomas N; Whelan, Sarah; Selfors, Laura M; Crowdis, Jett; Gray, G Kenneth; Bronson, Roderick T; Brenner, Dirk; Rufini, Alessandro; Dirksen, Robert T; Hezel, Aram F; Huber, Aaron R; Munger, Josh; Cravatt, Benjamin F; Vasiliou, Vasilis; Cole, Calvin L; DeNicola, Gina M; Harris, Isaac S.
Afiliação
  • Asantewaa G; Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Tuttle ET; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Ward NP; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Kang YP; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Kim Y; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Kavanagh ME; Department of Metabolism and Physiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 33612.
  • Girnius N; Department of Metabolism and Physiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 33612.
  • Chen Y; Department of Metabolism and Physiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 33612.
  • Duncan R; Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA, 92037.
  • Rodriguez K; Department of Cell Biology, Harvard Medical School, Boston, MA, USA, 02115.
  • Hecht F; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA, 06520.
  • Zocchi M; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Smorodintsev-Schiller L; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Scales TQ; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Taylor K; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Alimohammadi F; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Sechrist ZR; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Agostini-Vulaj D; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Schafer XL; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Chang H; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Smith Z; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • O'Connor TN; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Whelan S; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Selfors LM; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Crowdis J; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Gray GK; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Bronson RT; Department of Pharmacology and Physiology, University of Rochester, Rochester, NY, USA, 14642.
  • Brenner D; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Rufini A; Department of Surgery and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Dirksen RT; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Hezel AF; Department of Surgery and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Huber AR; Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Munger J; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Cravatt BF; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Vasiliou V; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Cole CL; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • DeNicola GM; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642.
  • Harris IS; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642.
bioRxiv ; 2023 Feb 11.
Article em En | MEDLINE | ID: mdl-36798186
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 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.
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article