Compensatory hyperphagia after fasting tracks recovery of liver energy status

Studies using metabolic inhibitors suggest that a reduction in hepatic ATP generates a stimulus that triggers feeding behavior. To investigate the relationship between changes in liver ATP and food intake under physiological conditions, we assessed changes in feeding behavior and liver adenine nucleotides during refeeding after 24 h of food deprivation. Deprived rats consumed 14 g of food in the first 3 h of refeeding; the rate of consumption declined markedly thereafter for the next 9 h, but remained higher than that seen in nonfasted rats. Fasting produced substantial reductions in ATP, ATP/ADP, and phosphorylation potential relative to fed levels. Refeeding restored liver ATP by 6 h, whereas ATP/ADP and phosphorylation potential did not fully recover until 12 h of refeeding. Restricting food intake during refeeding limited recovery of liver energy status. These results show that liver energy production recovers slowly during refeeding with a time course that parallels the compensatory change in eating behavior. These findings raise the possibility that changes in hepatic energy status play a role in satiation as well as in hunger.