A Western diet induced NAFLD in LDLR(-/)(-) mice is associated with reduced hepatic glutathione synthesis.

Title

A Western diet induced NAFLD in LDLR(-/)(-) mice is associated with reduced hepatic glutathione synthesis.

Creator

Li Ling; Zhang Guo-Fang; Lee Kwangwon; Lopez Rocio; Previs Stephen F; Willard Belinda; McCullough Arthur; Kasumov Takhar

Publisher

Free radical biology & medicine

Date

2016
2016-07

Description

Oxidative stress plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Glutathione is the major anti-oxidant involved in cellular oxidative defense, however there are currently no simple non-invasive methods for assessing hepatic glutathione metabolism in patients with NAFLD. As a primary source of plasma glutathione, liver plays an important role in interorgan glutathione homeostasis. In this study, we have tested the hypothesis that measurements of plasma glutathione turnover could be used to assess the hepatic glutathione metabolism in LDLR(-/)(-) mice, a mouse model of diet-induced NAFLD. Mice were fed a standard low fat diet (LFD) or a high fat diet containing cholesterol (a Western type diet (WD)). The kinetics of hepatic and plasma glutathione were quantified using the (2)H2O metabolic labeling approach. Our results show that a WD leads to reduced fractional synthesis rates (FSR) of hepatic (25%/h in LFD vs. 18%/h in WD, P\textless0.05) and plasma glutathione (43%/h in LFD vs. 21%/h in WD, P\textless0.05), without any significant effect on their absolute production rates (PRs). WD-induced concordant changes in both hepatic and plasma glutathione turnover suggest that the plasma glutathione turnover measurements could be used to assess hepatic glutathione metabolism. The safety, simplicity, and low cost of the (2)H2O-based glutathione turnover approach suggest that this method has the potential for non-invasive probing of hepatic glutathione metabolism in patients with NAFLD and other diseases.

Subject

*Flux; *Glutathione; *Heavy water; *Mass spectrometer; *NAFLD; *NASH; *Oxidative stress; *Western Diet; Animal; Animals; Antioxidants/metabolism; Diet; Disease Models; Glutathione/blood/*metabolism; Humans; LDL/blood/*genetics/metabolism; Liver/*metabolism/pathology; Mice; Non-alcoholic Fatty Liver Disease/blood/*genetics/pathology; Oxidative Stress/genetics; Receptors; Western/adverse effects

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

13–21

Volume

96

Citation

Li Ling; Zhang Guo-Fang; Lee Kwangwon; Lopez Rocio; Previs Stephen F; Willard Belinda; McCullough Arthur; Kasumov Takhar, “A Western diet induced NAFLD in LDLR(-/)(-) mice is associated with reduced hepatic glutathione synthesis.,” NEOMED Bibliography Database, accessed July 30, 2021, https://neomed.omeka.net/items/show/3568.

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