The effects of intermittent fasting on liver physiology and metabolism in mice

Abstract

Background: Intermittent fasting, as an emerging diet concept, has been widely practiced in the global population. A broad spectrum of health benefits has been reported in animal models and in humans for intermittent fasting. However, the underlying mechanisms remain largely elusive. In this study, we aimed to explore the effects and potential mode-of-action of intermittent fasting in mouse models, with focus on the liver.Methods: C57BL/6 mice were divided into five groups of 8-14 each, including 30-days ad libitum group, 30-days intermittent fasting group, 60-days ad libitum group, 60-days intermittent fasting group and refeeding group (30-days intermittent fasting followed by 30-days ad libitum). The food intake, body weight, liver weight and the blood biochemical parameters were detected. Targeted metabolic profiling of liver was performed.Results: We found that daily 12-hour intermittent fasting for one or two months significantly reduced the cumulative food intake, compared with the mice fed ad libitum. Fasting resulted in significantly reduced liver weight, with minimal effect on body weight. This effect on the liver by one month fasting could not be reversed by following one-month ad libitum feeding. Among the measured blood biochemical parameters, glucose level was decreased, while alkaline phosphatase was increased in the fasting mice. Surprisingly, targeted metabolic profiling revealed the global elevation of metabolites in the livers of fasting mice. These metabolic molecules include ATP, NADP, NADPH and succinate that are essentially involved in the citric acid cycle and oxidative phosphorylation. Conclusion: Daily 12-hour intermittent fasting for one to two months significantly reduced liver weight in mice, which is associated with enhanced liver metabolism.