Abstract

Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day) fasting or high fat diet (45% caloric supplied by fat) for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice). Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals.

Highlights

  • Obesity prevalence has been increased over the years

  • Our results showed that intermittent fasting improved learning and memory as measured by Barnes maze and fear conditioning

  • These results suggest that intermittent fasting improves brain functions and structures

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Summary

Introduction

Obesity prevalence has been increased over the years. About one third of American adults and 20% teenagers are obese [1,2]. Dietary restriction increases average and maximum life span [5,6] It decreases aging-related learning and memory impairments in animals and human [7,8]. Dietary restriction can stabilize the expression of synaptic protein expression to avoid aging-related changes [9]. These results suggest that dietary restriction attenuates the brain aging process. One method is to provide a food allotment that is about 60 – 70% of that consumed by control animals with ad libitum food This method is called caloric restriction and will usually result in significant decrease of body weight [10]. Intermittent fasting but not caloric restriction for 20 weeks increases hippocampal neuron tolerance to excitotoxic stress in mice, suggesting neuroprotective effects of intermittent fasting [10]

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