• obesity
• diabetes
• intermittent fasting

Background and aims: Worldwide, the prevalence of obesity has reached the level of an epidemic. Among the complications associated with metabolic diseases (obesity and type 2 diabetes), those affecting the central nervous system have raised important concern due to increased risks of neuropsychiatric diseases such as mood and cognitive disorders. Dietary restriction, particularly intermittent fasting (IF), that combines energy restricted and unrestricted days, improves insulin sensitivity and hyperglycemia. However, little is known about the effects of IF on brain function and plasticity in animal models of metabolic diseases. The aim of this thesis is to investigate how IF affects brain function and neural tissue transcriptional responses in a mouse model of diet induced obesity (DIO).

Materials and methods: 6-7 week-old male C57BL/6J mice were fed with high fat diet (60% Kcal from fat) for 10 weeks and then divided into four different experimental groups for the following 4-weeks: group #1 continued the HFD feeding (HFD), group #2 switched to an ad libitum balance diet (control chow, CC), group #3 was subjected to IF, eating every other day HFD (HFD-IF), group #4 was subjected to IF, eating every other day CC (CC-IF). Two further control groups of lean mice fed two different types of balanced diets were included.
The metabolic phenotype was evaluated by measuring the body weight, glycaemia, fat abundance and distribution, and plasmatic hormone levels.
Gene expression analysis was performed on occipital cortex, hippocampus and liver tissue.
The impact of different dietary regimens on mouse behavior was evaluated through 4 different behavioral tasks: Open Field Test (OFT), Object Recognition Test (ORT), Y-Maze and Elevated Plus Maze (EPM).

Results: Our preliminary results suggest that switching to IF or ad libitum CC after 10 weeks HFD significantly ameliorated glucose tolerance and decreased the body weight in DIO. Moreover, significant reduction in body fat was observed after CC or IF, but with increases in brown adipose tissue after CC-IF only. HFD showed a differential abundance in hormones known to play a crucial role in metabolism, fat distribution and appetite such as insulin and leptin.
Behavioral tests demonstrated that CC-IF is the strongest dietary regimen able to modulate mouse responses.
The gene expression analysis on cortex, hippocampus and liver demonstrated significant changes in the expression level of a variety of genes involved in plasticity and metabolic pathways.

Conclusion: The results collected so far suggest that CC-IF has the strongest effects on variation of all the parameters tested, with an amelioration of body weight and fat composition, glucose tolerance, and behavior in DIO mice.