Glutathione deficiency down-regulates hepatic lipogenesis in rats

<p>Abstract</p> <p>Background</p> <p>Oxidative 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.</p> <p>Results</p> <p>BSO 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.</p> <p>Conclusion</p> <p>This 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.</p

Comparing different early warning systems: Results from a horse race competition among members of the Macro-prudential Research Network

Over the recent decades researchers in academia and central banks have developed early warning systems (EWS) designed to warn policy makers of potential future economic and financial crises. These EWS are based on diverse approaches and empirical models. In this paper we compare the performance of nine distinct models for predicting banking crises resulting from the work of the Macroprudential Research Network (MaRs) initiated by the European System of Central Banks. In order to ensure comparability, all models use the same database of crises created by MaRs and comparable sets of potential early warning indicators. We evaluate the models’ relative usefulness by comparing the ratios of false alarms and missed crises and discuss implications for pratical use and future research. We find that multivariate models, in their many appearances, have great potential added value over simple signalling models. One of the main policy recommendations coming from this exercise is that policy makers can benefit from taking a broad methodological approach when they develop models to set macro-prudential instruments

Comparing different early warning systems: Results from a horse race competition among members of the Macro-prudential Research Network

Over the recent decades researchers in academia and central banks have developed early warning systems (EWS) designed to warn policy makers of potential future economic and financial crises. These EWS are based on diverse approaches and empirical models. In this paper we compare the performance of nine distinct models for predicting banking crises resulting from the work of the Macroprudential Research Network (MaRs) initiated by the European System of Central Banks. In order to ensure comparability, all models use the same database of crises created by MaRs and comparable sets of potential early warning indicators. We evaluate the models’ relative usefulness by comparing the ratios of false alarms and missed crises and discuss implications for pratical use and future research. We find that multivariate models, in their many appearances, have great potential added value over simple signalling models. One of the main policy recommendations coming from this exercise is that policy makers can benefit from taking a broad methodological approach when they develop models to set macro-prudential instruments

Comparing different early warning systems: Results from a horse race competition among members of the Macro-prudential Research Network

Over the recent decades researchers in academia and central banks have developed early warning systems (EWS) designed to warn policy makers of potential future economic and financial crises. These EWS are based on diverse approaches and empirical models. In this paper we compare the performance of nine distinct models for predicting banking crises resulting from the work of the Macroprudential Research Network (MaRs) initiated by the European System of Central Banks. In order to ensure comparability, all models use the same database of crises created by MaRs and comparable sets of potential early warning indicators. We evaluate the models’ relative usefulness by comparing the ratios of false alarms and missed crises and discuss implications for pratical use and future research. We find that multivariate models, in their many appearances, have great potential added value over simple signalling models. One of the main policy recommendations coming from this exercise is that policy makers can benefit from taking a broad methodological approach when they develop models to set macro-prudential instruments