Exacerbated oxidative stress in the fasting liver according to fuel partitioning

Abstract

Complete starvation may prove lethal due to excessive loss of body proteins. However, it is still not completely understood whether responses to food deprivation are time-dependently induced or triggered in relation with the successive phases of protein sparing and wasting that characterize prolonged fasting. As the liver has a wide range of vital functions, we examined the hepatic regulatory mechanisms elicited during prolonged fasting. We showed that fasting-induced transcriptome/proteome changes occur in close relation with fuel partitioning, independently of ATP levels. Omics data suggesting a worsening of oxidative stress during the proteolytic stage of fasting were further validated using biochemical assays. Low levels of antioxidant factors were indeed paralleled by their decreased activity that could be impaired by low NADPH levels. Oxidative damage to lipids and proteins was accordingly increased only during late fasting. At this stage, the gene/protein expression of several chaperones was also repressed. Together with the impairment of metabolic achievements, a vicious cycle involving protein misfolding and oxidative stress could jeopardize liver function when the proteolytic stage of fasting is reached. Thus, monitoring of liver impairments should help to better manage or treat catabolic and/or oxidative stress conditions, such as ageing and degeneration.

Short Period Starvation in Rat: The Effect of Aloe Vera Gel Extract on Oxidative Stress Status Ion

“…Fasting caused body weight loss and hypoglycemia and hypoinsulinemia (Godin and Wohaieb, 1988;Marczuk-Krynicka et al, 2003;Wasselin et al, 2014). Hypoglycemia increased lipid and protein metabolism (Wasselin et al, 2014). Thus, starvation results in decreased protein production and enzyme activities as well as increasing protein degeneration.…”

“…Thus, increasing production of ROS and H2O2 during starvation could decrease SOD and catalase activities. Fasting caused body weight loss and hypoglycemia and hypoinsulinemia (Godin and Wohaieb, 1988;Marczuk-Krynicka et al, 2003;Wasselin et al, 2014). Hypoglycemia increased lipid and protein metabolism (Wasselin et al, 2014).…”

“…Furthermore, fasting stimulated mitochondrial fatty acid oxidation and subsequently increased NADH production and its influx to TCA cycle. It caused electron transport chain to be more active and finally enhanced ROS generation (Wasselin et al, 2014). Sorensen and co-workers have shown 72 h starvation increased free radical production and changed membrane composition in rat liver (Sorensen et al, 2006).…”

“…Marczuk-Krynicka et al (2003) have shown catalase and SOD activities decreased in fasted rat livers but they did not alter in GPx activity in fasted rat livers. Wasselin et al (2014) evaluated gene expression and enzyme activities involved in the response to oxidative stress. They have shown a decrease in both catalase protein and its activity level in fasted rats.…”

“…Starvation decreased glucose plasma level. Lipid oxidation increased (Orellana et al, 1992;Wasselin et al, 2014) or was not changed (MarczukKrynicka et al, 2003) during starvation. Starvation has been reported to have pro-oxidative effect as a consequence of both elevated ROS generation and defeat in neutralization of ROS (Crescimanno et al, 1989;Domenicali et al, 2001;Robinson et al, 1997;Sorensen et al, 2006).…”