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Diet has a great impact on human health. Consumption of high caloric diet (rich in fat) may lead to obesity and metabolic disorders associated with inflammation. High fat diet (HFD) is associated with epidemic development of metabolic disorders. It can trigger dysbiosis which, may lead towards cellular stress development by increasing intestinal epithelial permeability, inflammation and metabolic syndrome. Manifestation of gut associated metabolic disorders may be causally linked with numerous chronic diseases such as, Inflammatory Bowel Disease (Crohn’s disease, Ulcerative colitis), Inflammatory Bowel Syndrome, insulin resistance and ultimately cancer. However, the exact mechanisms underlying HFD induced obesity remained unexplored. Thus, the current research was planned to evaluate the effects of HFD on different physiological aspects, pathophysiology of gut and metabolic stress. For this purpose HFD (15% and 30% Margarine: Blue Band®) feeding was done in Wistar rats for a period of 6 weeks (42 days). Blood sampling were thus done for evaluating lipid profile, serum glucose concentration and other biochemical analysis. Tissue sampling was conducted during different intervals of the experimental period to perform histopathology, fat staining, immunohistochemistry, cellular ROS and gene expression analysis. The data was statistically analyzed by two-way ANOVA and DMR. Results revealed significant role of HFD in elevating body weight (147.71±9.50 g), serum cholesterol (63.55±1.71 mg/dl), LDL (28.81±2.92 mg/dl) and triglycerides (70.05±2.51 mg/dl) compared to control group having body weight (137.24±6.11 g), serum cholesterol (52.48±0.84 mg/dl), LDL (19.25±2.57 mg/dl) and triglycerides (55.76±2.89 mg/dl) respectively. The onset of inflammation was observed in response to HFD feeding even after a short time period in gut. Apparently, the induction was triggered by HFD mediated stress response. The role of cellular stress pathways and calcium is crucial in underlying mechanism of ROS production, as high expression levels of MAPK-8, Traf-4, Traf-6, Calm-2, Grk-2 and Pias-2 genes were detected in HFD treatment groups as compared to that of control group. High E.coli count due to HFD consumption also demonstrated its role in alteration of gut microbiota. Overall, HFD has a major effect on different aspects of intestinal physiology and it induces obesity which is accompanied by oxidative stress due to alteration of gut physiology.
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