Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

BackgroundThere is growing recognition for a reciprocal, bidirectional link between anxiety disorders and obesity. Although the mechanisms linking obesity and anxiety remain speculative, this bidirectionality suggests shared pathophysiological processes. Neuroinflammation and oxidative damage are implicated in both pathological anxiety and obesity. This study investigates the relative contribution of comorbid diet-induced obesity and stress-induced anxiety to neuroinflammation and oxidative stress. MethodsThirty-six (36) male Lewis rats were divided into four groups based on diet type and stress exposure: 1) control diet unexposed (CDU) and 2) exposed (CDE), 3) Western-like high-saturated fat diet unexposed (WDU) and 4) exposed (WDE). Neurobehavioral tests were performed to assess anxiety-like behaviors. The catalytic concentrations of glutathione peroxidase and reductase were measured from plasma samples, and neuroinflammatory/oxidative stress biomarkers were measured from brain samples using Western blot. Correlations between behavioral phenotypes and biomarkers were assessed with Pearsons correlation procedures. ResultsWe found that WDE rats exhibited markedly increased levels of glial fibrillary acidic protein (185%), catalase protein (215%), and glutathione reductase (GSR) enzymatic activity (418%) relative to CDU rats. Interestingly, the brain protein levels of glutathione peroxidase (GPx) and catalase were positively associated with body weight and behavioral indices of anxiety. ConclusionsTogether, our results support a role for neuroinflammation and oxidative stress in heightened emotional reactivity to obesogenic environments and psychogenic stress. Uncovering adaptive responses to obesogenic environments characterized by high access to high-saturated fat/high-sugar diets and toxic stress has the potential to strongly impact how we treat psychiatric disorders in at-risk populations. HighlightsO_LIPredatory odor stress heightens footshock reactivity and anxiety-like behaviors in Lewis rats. C_LIO_LIWD intake increases glutathione reductase activity in plasma. C_LIO_LIWD intake and PS exposure acted synergistically to increase the brain protein levels of catalase and the glial fibrillary acidic protein. C_LIO_LIThe protein levels and activities of some redox/neuroinflammatory biomarkers are closely associated with behavioral proxies related to fear and anxiety in rats. C_LI