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Abstract
Consumption of a high-fat (HF) diet has been shown to increase risk of metabolic disorders such as obesity and diabetes. These comorbidities are a major health problem in westernized countries, including the United States, where HF diets are increasingly popular. Obesity has been long-defined as a chronic, low-grade, systemic inflammatory state and the integrity of the gastrointestinal (GI) tract has been found to contribute to this. Increased GI permeability due to changes in gut microbiota composition in response to HF diet allows for the translocation of pro-inflammatory bacterial byproducts, such as lipopolysaccharide (LPS). Currently, there is little research investigating potential diet interventions to maintain gut microbiota composition, preserve gut integrity and gut-brain satiety signaling. Therefore, the objective of this dissertation is to investigate the effects of diet interventions in prevention of the negative metabolic outcomes related to HF diet. I hypothesized that promoting a gut microbiota composition in rodents closer to a control low fat (LF) diet would attenuate the effects of HF diet. For both studies, male Wistar rats were fed a 45% HF diet for 7-8 weeks and either supplemented with a prebiotic (potato resistant starch, Chapter 2) or pair-fed to modulate timing of feeding (Chapter 3). For both studies, weight and food intake, microbiota composition, inflammatory status, glucose homeostasis, satiety response and vagal signaling were assessed. In the potato study (Chapter 2), resistant starch (RS) supplementation prevented microbiota dysbiosis and HF diet-induced inflammation. Functionally, RS prevented hyperphagia, loss in glucose homeostasis, satiety sensitivity and hindbrain unmyelinated c fibers associated with HF diet. In the second study (Chapter 3), timing of feeding, regardless of diet composition, was shown to favorably manipulate microbiota composition. Rats pair-fed HF diet just before the onset of their active (dark) cycle ate the same calories but consumed significantly fewer meals. Pair-feeding improved microbiota dysbiosis, inflammation status and glucose tolerance associated with HF diet. The studies of this dissertation suggest that microbiota manipulation via prebiotic supplementation or feeding pattern modulation preserve gut microbiota composition, preventing low-grade systemic inflammation associated with loss in glucose homeostasis and satiety signaling, avoiding the onset of obesity and other metabolic disorders.