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Abstract
Vagal afferent neurons (VAN) are uniquely positioned in the lamina propria of the gastrointestinal (GI) tract and can receive and transmit both nutrient and microbiota derived signals from the GI tract to the central nervous system (CNS). Changes in the gut microbiota are associated with changes in diet, diet-induced obesity (DIO) and changes in host feeding behavior. Changes in responding to GI-originating nutrient-induced signals, notably cholecystokinin (CCK), are also associated DIO and can potentially drive the initiation of hyperphagia that leads to obesity.
Chapter 4 demonstrates that changes in diet associated with the development of obesity alter gut microbiota composition and brain structures involved with regulation of feeding. High fat (HF) and high sugar (HS) diets are associated with the development of obesity and inflammation in the nodose ganglion (NG) and nucleus of the solitary tract (NTS) and remodeling of VAN projections to the NTS. This chapter demonstrates that addition of gut microbe supporting compounds such as resistant starch to an obesogenic diet result in decreased aberrations in gut microbiota composition and the gut brain signaling anatomy.
Chapter 5, the first study to investigate a role for gram-positive bacterial metabolites in the development of NG inflammation, provides support for an important role for immune cell types, including microglia and macrophages, in the response to metabolites associated with the development of DIO.
Chapter 6 presents a novel method of microglia/macrophage depletion in the NG. Injection of clodronate liposomes into NG effectively depletes microglia/macrophages for up to six days. In response to introduction of a 60% HF diet, depletion of NG microglia/macrophages prevents HF diet-induced hyperphagia, weight gain and maintains the food-intake reductions associated with administration of exogenous CCK.
In total, this body of work supports existing findings that the development of inflammation is involved in the development of obesity. Furthermore, we identify a role for NG microglia/macrophages in HF diet-induced hyperphagia. These results support additional work into the potential for modulation of these immune cell responses to combat over consumption of energy dense diets and the development of obesity.
Chapter 4 demonstrates that changes in diet associated with the development of obesity alter gut microbiota composition and brain structures involved with regulation of feeding. High fat (HF) and high sugar (HS) diets are associated with the development of obesity and inflammation in the nodose ganglion (NG) and nucleus of the solitary tract (NTS) and remodeling of VAN projections to the NTS. This chapter demonstrates that addition of gut microbe supporting compounds such as resistant starch to an obesogenic diet result in decreased aberrations in gut microbiota composition and the gut brain signaling anatomy.
Chapter 5, the first study to investigate a role for gram-positive bacterial metabolites in the development of NG inflammation, provides support for an important role for immune cell types, including microglia and macrophages, in the response to metabolites associated with the development of DIO.
Chapter 6 presents a novel method of microglia/macrophage depletion in the NG. Injection of clodronate liposomes into NG effectively depletes microglia/macrophages for up to six days. In response to introduction of a 60% HF diet, depletion of NG microglia/macrophages prevents HF diet-induced hyperphagia, weight gain and maintains the food-intake reductions associated with administration of exogenous CCK.
In total, this body of work supports existing findings that the development of inflammation is involved in the development of obesity. Furthermore, we identify a role for NG microglia/macrophages in HF diet-induced hyperphagia. These results support additional work into the potential for modulation of these immune cell responses to combat over consumption of energy dense diets and the development of obesity.