Effects of intermittent fasting on liver physiology and metabolism in mice

Abstract

A broad spectrum of health benefits from intermittent fasting have been reported in studies on animal models and human subjects. However, the underlying mechanisms of these beneficial effects remain largely elusive. The present study aimed to explore the effects and potential mode of action of intermittent fasting in mouse models with a focus on the liver. C57BL/6 mice were subjected to intermittent fasting or <i>ad libitum</i> feeding as controls. It was determined that 12 h of daily intermittent fasting for 30 days significantly reduced the cumulative food intake compared with that in mice with <i>ad libitum</i> feeding. Fasting resulted in a significantly reduced liver mass but only had a minimal effect on bodyweight. The effects on the liver by 30 days of fasting were not reversed by subsequent <i>ad libitum</i> refeeding for 30 days. Among the measured blood biochemical parameters, the levels of blood glucose were decreased, while the levels of alkaline phosphatase were increased in fasting mice. Of note, targeted metabolic profiling revealed global elevation of metabolites in the livers of fasting mice. These metabolic molecules included adenosine triphosphate, nicotinamide adenine dinucleotide phosphate (NADP), reduced NADP and succinate, which are essentially involved in the citric acid cycle and oxidative phosphorylation. Thus, it was concluded that daily 12 h of intermittent fasting for one month significantly reduced the liver weight of mice, which is associated with enhanced liver metabolism.