Cyclic Intermittent Fasting Influences the Structure of Hepatocyte Nuclear Membrane in Young and Old Rats

Aims: The present study was undertaken to monitor the changes in structural and dynamic state of hepatocyte nuclear membrane of young (3-months) and old (20-months) rats subjected to intermittent fasting (IF).

Study Design: young (3-month) and old (20-month) rats were individually housed and randomly assigned to one of five groups (with 10 rats per group): (Control)-fed Ad libitum; (1IF)-provided access to a limited amount of food (4g/100g and 2g/100g of food/body weight for young and old rats, respectively) every other day for 10 days; (1R)-refeeded Ad libitum for 20 days after 1IF; (2IF)-provided the same regimen as for 1IF but after successive 1IF and 1R; (2R)-refeeded Ad libitum for 10 days after 2IF.

Methodology: The magnitude of fluidity changes was evaluated through measuring the excimer-to-monomer intensity ratio (E/M) in the pyrene emission spectra. The changes in membrane hydration were assessed using Laurdan generalized polarization (GP).

Results: During two cycles of intermittent fasting/refeeding statistically significant differences in E/M for young animals are observed only after the first refeeding (increase by 11% compared to control). 1IF and 1R in old animals were followed by ~26% and ~18% decrease in E/M value. The second cycle of dietary regimen brought about ~20% and ~36% decrease in E/M of old rats after 2IF and 1R, respectively. The first intermittent fasting resulted in ~74% and ~101% increase in GP value of young and old rats, respectively, and the refeeding period GP parameter underwent ~221% and ~89% increase in comparison with control for young and old rats, respectively. After the second IF following the first refeeding the young and old rats were characterized by ~200% and ~44% increase in GP, respectively. On the contrary, second refeeding leads to ~182% and ~27% increase in GP for young and old rats, respectively.

Conclusion: The main outcome reached is the identification of differences in the effects of re-applicated IF on nuclear membrane fluidity and hydration in animals of different age, suggesting that membrane responses to IF are governed by age-dependent mechanisms.