EVIDENCE OF OBESITY-RELATED BRAIN INJURY IN DIET-INDUCED OBESITY (DIO) RATS: MACRO- AND MICRO-ANATOMICAL ANALYSIS.

Obesity is an excessive or abnormal accumulation of adipose tissue due to a high-caloric diet and/or reduced physical activity. Statistical analysis revealed that more than 2 billion people worldwide are overweight and of these over 600 million are obese. Obesity is now considered more and more a medical challenge. Furthermore obesity may involve the development of chronic diseases such as cerebrovascular diseases promoting a cognitive decline. Caloric-dense diet-induced obesity (DIO), represents an interesting animal model showing several common features with human obesity. DIO rats of 7 weeks of age exposed to high fat diet (45%) at libitum after 5 weeks develop the obese phenotype. For explaining the relationship between obesity and nervous system changes, DIO rats were studied after 5 weeks and 17 weeks of high fat diet. CHOW rats were used for comparison. During and at the end of treatment, memory performance was assessed with different cognitive tests. Ultrasonographic (US) and computer tomography (CT) techniques were used to detect adipose tissue accumulation. Magnetic Resonance Imaging (MRI) was used to highlight brain morphological changes. Frontal cortex and hippocampus microanatomical changes were assessed by immunohistochemical techniques. Our results confirmed the development of obesity after 5 weeks of fat diet. After long-term (17 weeks) high fat diet exposure, body weight values were remarkably increased compared to the control group and younger DIO rats. In DIO rats a reduction of a retention latency time in the emotional learning task was noticeable. US and CT analysis revealed an increase of deposition of both visceral and subcutaneous adipose tissue and a decrease of hepatic attenuation in older DIO rats. MRI did not show significant morphological and vascular brain changes. Immunohistochemical and immunochemical analysis showed an increased expression of glial-fibrillary acid protein (GFAP) in the frontal cortex and hippocampus of older DIO rats compared to age-matched CHOW rats. A decrease of neuronal specific nuclear protein (NEU-N) was found in 17-week-old DIO rats compared to control CHOW primarily in the hippocampus. These findings show that the development of obesity, although not accompanied by macroscopic brain changes, is accompanied to a brain injury characterized by astrogliosis and neurodegeneration. The discovery of the above changes in the brain of DIO rats represents the first step to better clarify obesity-related brain injury and may contribute to identify therapeutic and nutritional strategies to prevent target organ damage.