Glutathione deficiency down-regulates hepatic lipogenesis in rats

Lipids in Health and Disease

Research

Kristin Weiße¹  Tobias Schmidt¹  Andreas S Mueller¹  Corinna Brandsch¹  Gabriele I Stangl¹  Diana Behn¹ 

[1] Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Von-Danckelmann-Platz 2, D-06120, Halle (Saale), Germany;

关键词: High Density Lipoprotein;    G6PDH Activity;    Hepatic Lipogenesis;    Buthionine Sulfoximine;    XBP1 mRNA;   

DOI  :  10.1186/1476-511X-9-50

 received in 2010-04-08, accepted in 2010-05-19,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundOxidative stress is supposed to increase lipid accumulation by stimulation of hepatic lipogenesis at transcriptional level. This study was performed to investigate the role of glutathione in the regulation of this process. For that purpose, male rats were treated with buthionine sulfoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase, for 7 days and compared with untreated control rats.ResultsBSO treatment caused a significant reduction of total glutathione in liver (-70%), which was attributable to diminished levels of reduced glutathione (GSH, -71%). Glutathione-deficient rats had lower triglyceride concentrations in their livers than the control rats (-23%), whereas the circulating triglycerides and the cholesterol concentrations in plasma and liver were not different between the two groups of rats. Livers of glutathione-deficient rats had lower mRNA abundance of sterol regulatory element-binding protein (SREBP)-1c (-47%), Spot (S)14 (-29%) and diacylglycerol acyltransferase 2 (DGAT-2, -27%) and a lower enzyme activity of fatty acid synthase (FAS, -26%) than livers of the control rats. Glutathione-deficient rats had also a lower hepatic activity of the redox-sensitive protein-tyrosine phosphatase (PTP)1B, and a higher concentration of irreversible oxidized PTP1B than control rats. No differences were observed in protein expression of total PTP1B and the mature mRNA encoding active XBP1s, a key regulator of unfolded protein and ER stress response.ConclusionThis study shows that glutathione deficiency lowers hepatic triglyceride concentrations via influencing lipogenesis. The reduced activity of PTP1B and the higher concentration of irreversible oxidized PTP1B could be, at least in part, responsible for this effect.

【 授权许可】

Unknown   
© Brandsch et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.