Hypothalamic expression of inflammatory mediators in an animal model of binge eating

Binge eating episodes are characterized by uncontrollable, distressing eating of a large amount of highly palatable food and represent a central feature of bingeing related eating disorders. Research suggests that inflammation plays a role in the onset and maintenance of eating-related maladaptive behavior. Markers of inflammation can be selectively altered in discrete brain region where they can directly or indirectly regulate food intake. In the present study we measured expression levels of different components of cytokine systems (IL-1, IL-6, IL-18, TNF-\uf061 and IFN-&3) and related molecules (iNOS and COX2) in the preoptic and anterior-tuberal parts of the hypothalamus of a validated animal model of binge eating. In this animal model, based on the exposure to both food restriction and frustration stress, binge-like eating behavior for highly palatable food is not shown when animals are exposed to the frustration stress during the estrus phase. We found a characteristic down-regulation of the IL-18/ IL-18 receptor system (with increased expression of the inhibitor of the pro-inflammatory cytokine IL18, IL-18BP, together with a decreased expression of the binding chain of the IL-18 receptor) and a three-fold increase in the expression of iNOS specifically in the anterior- tuberal region of the hypothalamus of animals that develop a binge-like eating behavior. Differently, when food restricted animals were stressed during the estrus phase IL-18 expression increased while iNOS expression was not significantly affected. Considering the role of this region of the hypothalamus in controlling feeding related behavior, this can be relevant in eating disorders and obesity. Our data suggest that by targeting centrally selected inflammatory markers, we may prevent that disordered eating turns into a full blown eating disorder

Brain Alterations in High Fat Diet Induced Obesity: Effects of Tart Cherry Seeds and Juice

Evidence suggests that obesity adversely affects brain function. High body mass index, hypertension, dyslipidemia, insulin resistance, and diabetes are risk factors for increasing cognitive decline. Tart cherries (Prunus Cerasus L.) are rich in anthocyanins and components that modify lipid metabolism. This study evaluated the effects of tart cherries on the brain in diet-induced obese (DIO) rats. DIO rats were fed with a high-fat diet alone or in association with a tart cherry seeds powder (DS) and juice (DJS). DIO rats were compared to rats fed with a standard diet (CHOW). Food intake, body weight, fasting glycemia, insulin, cholesterol, and triglycerides were measured. Immunochemical and immunohistochemical techniques were performed. Results showed that body weight did not differ among the groups. Blood pressure and glycemia were decreased in both DS and DJS groups when compared to DIO rats. Immunochemical and immunohistochemical techniques demonstrated that in supplemented DIO rats, the glial fibrillary acid protein expression and microglial activation were reduced in both the hippocampus and in the frontal cortex, while the neurofilament was increased. Tart cherry intake modified aquaporin 4 and endothelial inflammatory markers. These findings indicate the potential role of this nutritional supplement in preventing obesity-related risk factors, especially neuroinflammation

A multidisciplinary approach to study the brain injury in Diet-Induced Obesity (DIO) rats

Obesity represents an independent risk factor for the development of cerebrovascular disease and cognitive impairment. The systemic effects, such as increased fat mass, hypertension, insulin resistance and general metabolic dysfunction, have been identified as factors that may lead to impaired cognitive function. To clarify the possible relationships between obesity and nervous system changes, high-caloric Diet-Induced Obesity (DIO) rats 7 weeks-old, were studied after 17 weeks of hypercaloric diet compared to control rats with not fat diet (Chow) or to rats not developing obesity (DIO-resistant DR). Food consumption, fat mass content, blood pressure and blood parameters were assessed. Different behavioural tests were used to estimate cognitive performance. RT-qPCR, immunochemical and immunohistochemical analysis were performed to evaluate neuronal, glial and vascular markers. The obese phenotype developd after 5 weeks of high fat diet exposure and body weight values remained higher in DIO rats compared to the control group and DR rats during the treatment. Systolic blood pressure, glycaemia and insulin were higher in DIO rats only after 17 weeks. No differences in values of total cholesterol and triglycerides were observed. Furthermore increase of thiobarbituric reactive substances and increase of oxidated proteins, was observed in the serum of DIO rats compared to Chow rats. The open-field test revealed, in the older DIO rats, a decrease of cumulative distance travelled and in the number of rearings and an increase of total immobility time. Older DIO rats only, showed a reduction of retention latency time in the passive avoidance test. RT-qPCR, immunochemical and immunohistochemical analysis showed an increased expression of the glial-fibrillary acid protein in the frontal cortex and hippocampus of older DIO rats compared to age-matched Chow and DR rats. A decrease of neurofilament expression was found in the hippocampus of older DIO rats without changes in the number of neurons. A modulation in the Transient Receptor Potential (TRP) channels and synaptic components was highlighted in cerebral areas. These results indicate that obesity in rats, in addition to the development of correlate cerebrovascular risk factors, causes brain injury characterized by astrogliosis, neurodegeneration and impaired learning and memory tasks. The identification of neurodegenerative changes in DIO rats may represent the first step to better characterize the neuronal modifications occurring in the obesity and propose pharmacological treatments or food strategies to counter them

Obesity-related nervous system injury: preliminary evidences in diet induced obesity (DIO) rats.

Increased food intake, reduced physical activity and altered metabolic processes are the variables that affect energy balance inducing obesity. Obesity is now considered an increas-ingly medical challenge. Actually, the prevalence of obesity has increased dramatically worldwide over the last decades and has now reached epidemic proportions. On the other hand, obesity is associated with the development of chronic diseases such as cerebrovascu-lar disease promoting the cognitive decline. Caloric-dense diet induced obesity (DIO), provides a useful animal model sharing several common features with human obesity. DIO rats of 7 weeks of age are expose to high fat (45 %) diet ad libitum and after 5 weeks the obese phenotype starts to be develop. To clarify the possible relationships between obesity and nervous system changes, DIO rats were studied after 5 weeks and 17 weeks of hypercaloric diet compared to the control rats with not fat diet (Chow). Memory performance were measured using different cognitive tests. Moreover, ultrasonographic (US) and computed tomography (CT) evaluations were per-formed to detect adipose tissue changes. Magnetic resonance imaging (MRI) to highlight brain morphological alterations was used. Morphological changes of brain areas (frontal cor-tex, hippocampus) were evaluated by immunohistochemical analysis. The results confirmed the developed of obesity after 5 weeks of fat diet. At long-term (17 weeks) high fat diet exposure, rats increased significantly their body weight in comparison to the control group and the youngest DIO rats. The US and CT analysis indicated an increase of deposition of both visceral and subcutaneous adipose tissue and evidences a decrease of hepatic attenuation in the older DIO rats.MRI images did not show vascular and morphologi-cal alterations in brain. Instead, immuhistochemical and immunochemical analysis, revealed an increase expression of glial-fibrillary acidic protein (GFAP) in the older DIO rats compared to the age- matched Chow rats both in frontal cortex and in hippocampus. DIO rats showed a reduction of retention latency time in the emotional learning task. These preliminary findings indicate that the development of obesity, does not determined gross anatomy alteration in brain, but the occurrence of injury characterized by astrogliosis. The identification of neurodegenerative changes in DIO may represent the first insight to better characterize the neuronal involvement in obesity

Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption

Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin-releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF-1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF-1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge-eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds