Decreased mitochondrial metabolic requirements in fasting animals carry an oxidative cost

Many animals experience periods of food shortage in their natural environment. It has been hypothesised that the metabolic responses of animals to naturally‐occurring periods of food deprivation may have long‐term negative impacts on their subsequent life‐history. In particular, reductions in energy requirements in response to fasting may help preserve limited resources but potentially come at a cost of increased oxidative stress. However, little is known about this trade‐off since studies of energy metabolism are generally conducted separately from those of oxidative stress. Using a novel approach that combines measurements of mitochondrial function with in vivo levels of hydrogen peroxide (H2O2) in brown trout (Salmo trutta), we show here that fasting induces energy savings in a highly metabolically active organ (the liver) but at the cost of a significant increase in H2O2, an important form of reactive oxygen species (ROS). After a 2‐week period of fasting, brown trout reduced their whole‐liver mitochondrial respiratory capacities (state 3, state 4 and cytochrome c oxidase activity), mainly due to reductions in liver size (and hence the total mitochondrial content). This was compensated for at the level of the mitochondrion, with an increase in state 3 respiration combined with a decrease in state 4 respiration, suggesting a selective increase in the capacity to produce ATP without a concomitant increase in energy dissipated through proton leakage. However, the reduction in total hepatic metabolic capacity in fasted fish was associated with an almost two‐fold increase in in vivo mitochondrial H2O2 levels (as measured by the MitoB probe). The resulting increase in mitochondrial ROS, and hence potential risk of oxidative damage, provides mechanistic insight into the trade‐off between the short‐term energetic benefits of reducing metabolism in response to fasting and the potential long‐term costs to subsequent life‐history traits