This research investigated the role of the intestinal microbiota in shaping host food intake and body weight through immunomodulation, the impact of refined and unrefined diets, and though fermentable fibre induced gastrointestinal hormone secretion. Gut-derived lipopolysaccharide activating TLR4 has been proposed to contribute to obesity. To investigate this, TLR4-/- or CD14-/- mice and C57BL/6J controls were fed a high-fat or low-fat diet. Neither TLR4-/- or CD14-/- were protected against high-fat diet-induced obesity. High-fat diet increased hypothalamic expression of SerpinA3N and SOCS3 regardless of genotype; however, inflammatory gene expression was not increased. To investigate the use of chow control diets in obesity-associated microbiota changes, C57BL/6J mice were fed a chow diet, refined high-fat, or low-fat diet. Both high-fat and low-fat refined diets resulted in similar dramatic alterations in the composition of the intestinal microbiota at the phylum, family, and species level compared to chow, while only high-fat diet feeding resulted in obesity and glucose intolerance. The roles of colonic GLP-1 and PYY in mediating fermentable fibre in reducing food intake and body fat were investigated using GLP-1R-/- and PYY-/- mice fed a high-fat diet supplemented with inulin or cellulose. Inulin supplementation reduced body fat and food intake in C57BL/6J control mice while GLP-1R-/- and PYY-/- mice showed an attenuated response to dietary inulin. In summary, this research questions the role of TLR4 and LPS in diet-induced obesity. These results demonstrate the importance of the control diet used in studies of obesity in mice and indicate that many of the obesity-associated changes in the gut microbiota are due to comparing refined high-fat diets with chow diets. These results also provide evidence for an essential role for both GLP-1 and PYY in mediating the food intake and bodyweight-reducing effects of fermentable fibre.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:720578 |
| Date | January 2016 |
| Creators | Dalby, Matthew John |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=232362 |
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