Obesity and Age-Related Changes in the Brain of the Zucker Lepr fa/fa Rats.

Daniele Tomassoni,Carlo Cifani,Michele Moruzzi,Seyed Khosrow Tayebati,Maria Vittoria Micioni Di Bonaventura,Ilenia Martinelli,Francesco Amenta

doi:10.3390/nu12051356

Abstract

Metabolic syndrome (MetS) is an association between obesity, dyslipidemia, hyperglycemia, hypertension, and insulin resistance. A relationship between MetS and vascular dementia was hypothesized. The purpose of this work is to investigate brain microanatomy alterations in obese Zucker rats (OZRs), as a model of MetS, compared to their counterparts lean Zucker rats (LZRs). 12-, 16-, and 20-weeks-old male OZRs and LZRs were studied. General physiological parameters and blood values were measured. Immunochemical and immunohistochemical techniques were applied to analyze the brain alterations. The morphology of nerve cells and axons, astrocytes and microglia were investigated. The blood–brain barrier (BBB) changes occurring in OZRs were assessed as well using aquaporin-4 (AQP4) and glucose transporter protein-1 (GLUT1) as markers. Body weight gain, hypertension, hyperglycemia, and hyperlipidemia were found in OZRs compared to LZRs. In the frontal cortex and hippocampus, a decrease of neurons was noticeable in the older obese rats in comparison to their age-matched lean counterparts. In OZRs, a reduction of neurofilament immunoreaction and gliosis was observed. The BBB of older OZRs revealed an increased expression of AQP4 likely related to the development of edema. A down-regulation of GLUT1 was found in OZRs of 12 weeks of age, whereas it increased in older OZRs. The behavioral analysis revealed cognitive alterations in 20-week-old OZRs. Based on these results, the OZRs may be useful for understanding the mechanisms through which obesity and related metabolic alterations induce neurodegeneration.

Highlights

Low physical exercise, and impaired metabolic activities are responsible for energy imbalance that leads to obesity
Overall analysis of variance (ANOVA) showed that food intake was higher in obese Zucker rats (OZRs) compared to lean Zucker rats (LZRs) (p < 0.001)
We found a significant decrease in the locomotor activity of OZRs since 12 weeks of observation, reflected by the lowest number of ambulatory and vertical counts compared to LZRs

Summary

Introduction

Low physical exercise, and impaired metabolic activities are responsible for energy imbalance that leads to obesity. Metabolic syndrome (MetS) is a multifactorial syndrome caused by an insulin resistance followed by abnormal adipose tissue deposition and function. Arterial hypertension, hyperglycemia, hypertriglyceridemia, HDL cholesterol reduction, and abdominal obesity are common clinical manifestations. MetS is a hazard factor for developing diabetes, fatty liver, coronary heart disease, oncological pathologies, and brain injury [1,2]. Epidemiological studies consider MetS and its distinctive aspects as a cause of the increase of cardiovascular and cerebrovascular diseases, as well as mortality [3,4,5].

Objectives

Methods

Results

Discussion

Conclusion