- Title
- Fatty acids and the innate immune responses
- Creator
- Li, Qian
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2017
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- The management and control of asthma remains a complex issue. Increasing focus is being given to the non-genetic, environmental factors which appear likely to be contributing to asthma. The link between asthma and obesity has been investigated in numerous epidemiologic studies, however the mechanisms of association are not fully elucidated. Recently, more attention has been focused on dietary patterns and nutrient intake and their relationship with asthma, as well as their ability to induce both pro and anti-inflammatory immune responses in asthma. Consumption of a high energy mixed meal, as commonly consumed by obese asthmatics, increases neutrophilic airway inflammation in asthmatic subjects. In Chapter III of this thesis, we used microarray techniques to examine the molecular mechanisms driving airway neutrophilia following a high energy mixed meal in asthmatics. Our data identified changes in inflammatory gene expression that may contribute to increased postprandial airway neutrophilia and may provide useful therapeutic targets for immunomodulation. This may be particularly relevant to obese asthmatics, who are habitually consuming diets with a high fat content. In Chapter IV, we investigated the differences in airway inflammation in non-obese versus obese asthmatics, using nanostring technology; another technique for examining expression of large numbers of genes. Our data identified several genes and potential pathways that contribute to the different responses of obese asthmatics compared with non-obese asthmatics and highlights several genes targets that could be furthered explored in order to develop improved therapies for managing obese asthma. In Chapter V, we examined acute effects of saturated fatty acids, omega-6 PUFA and simple carbohydrates on systemic and airway inflammation in asthma. In addition, we compared the postprandial effect of these nutrients in obese versus non-obese asthmatics. Our data showed that saturated fatty acids have the most potent inflammatory effects, both systemically and in the airways. Furthermore, while obese asthmatics have minimal changes in airway inflammation following a saturated fat challenge, non-obese asthmatics have a significantly increased degree of airway neutrophilia following a saturated fat challenge. Gene expression profiling identified a number of inflammatory pathways that are activated in the airways following a saturated fat meal, involving toll-like receptors and the NLRP3 inflammasome. This thesis sheds light on the inflammatory effects of high energy food, as well as individual macronutrients, in the airways of asthmatics. We have also identified specific molecular pathways that are driving these effects. This research highlights that for non-obese asthmatics, restriction of dietary saturated fat intake may be beneficial in reducing fat-induced neutrophilic airway inflammation, while for those obese patients, an effective approach may involve therapeutics that target the NLRP3 inflammasome.
- Subject
- asthma; obesity; fatty acid
- Identifier
- http://hdl.handle.net/1959.13/1335816
- Identifier
- uon:27504
- Rights
- Copyright 2017 Qian Li
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 2 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 351 KB | Adobe Acrobat PDF | View Details Download |