- Title
- Approaches to reducing inflammation in obesity: an investigation into the effects of short chain fatty acids
- Creator
- Eslick, Shaun Roy
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2022
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- The presence of obesity has dramatically risen worldwide, where currently, approximately 13% of the world’s population is classed as obese.(1) In Australia, statistics have revealed that approximately every 2 in 3 adults over the age of 18 years are overweight or obese.(2). Overweight and obesity significantly increase the risk of developing a number of chronic health diseases such as cardiovascular disease, type 2 diabetes, insulin resistance, liver disease and some types of cancer.(3) Current evidence within the literature suggests that the development of numerous obesity-related chronic diseases is linked to chronic low grade systemic inflammation.(4) Therefore, strategies that decrease obese systemic inflammation are paramount in order to reduce the risk and burden of obesity-related chronic disease. In obesity, systemic inflammation is largely driven by rapid growth of adipose tissue as a result of excess energy intake. In lean subjects, adipose tissue contains immune cells that play vital roles in the removal of dead cells, cell debris and perform maintenance of tissue homeostasis. (5) In obesity, as a result of excess fat accumulation, changes in the number and function of immune cells occurs, particularly to macrophages.(5) In the obese state, macrophages undergo a phenotypic switch from M2 macrophages, characterised by anti-inflammatory properties, to M1 macrophages, typically considered pro-inflammatory.(6, 7) M1 phenotype macrophages are unable to sufficiently perform lipid buffering, resulting in the spill over of lipids into circulation, triggering activation of inflammatory cascades.(7) Another key feature of obesity is metabolic endotoxemia, a condition characterised by elevated levels of endotoxins such as lipopolysaccharides. Lipopolysaccharides also drive obese systemic inflammation via stimulation of pro-inflammatory pathways and subsequently production of pro-inflammatory cytokines.(8) The most obvious strategy for attenuating chronic low grade systemic inflammation in obesity is weight loss. Whilst the literature has shown that weight loss can reduce systemic inflammation in obesity, few studies have characterised how weight loss achieves these reductions. In Chapter 2, we show that systemic inflammation is present in obesity and highlight the mechanistic pathways that lead to changes to systemic inflammation that occur with weight loss. Secondly, this thesis investigated a dietary approach to attenuating obese systemic inflammation. Chapter 3 presents the current evidence for the effect of SCFAs and prebiotics on systemic inflammation in obesity. This systematic review and meta-analysis showed that evidence from human studies is conflicting whereby approximately 45% of studies in humans reported a significant decrease in one or more inflammatory biomarkers as a result of SCFA or prebiotic supplementation. In contrast, this review found that the effects of SCFAs and prebiotics were more conclusive in animal studies where approximately 90% of studies saw a significant reduction in one or more biomarkers of inflammation. Whilst this review highlighted the need for more studies to be undertaken in humans, it provides supportive evidence for the use of SCFAs as a novel treatment for obese systemic inflammation. Finally, in chapter 4 we examined an in-vitro model to explore the anti-inflammatory effects of SCFAs on immune cells isolated from obese subjects. In this model, we demonstrated that the SCFAs, acetate, butyrate and propionate, were successful in reducing production of pro-inflammatory cytokines as well as inducing a number of molecular changes to pro-inflammatory pathways. Furthermore, this model provided insight into the mechanisms driving the anti-inflammatory effects of SCFAs in obese systemic inflammation. The research undertaken in this thesis offers insight into two effective strategies for attenuating chronic low-grade systemic inflammation that occurs in obesity. This thesis provides insight into the changes that occur to obese systemic inflammation with weight loss and highlights evidence for the use of SCFAs as a novel dietary approach for the reduction of obese systemic inflammation. This research shows approaches for reducing chronic low grade systemic inflammation and therefore approaches to reduce the burden of obesity-related chronic disease.
- Subject
- obesity; systemic inflammation; weight loss; short chain fatty acids; free fatty acids; histone deacetylase
- Identifier
- http://hdl.handle.net/1959.13/1513262
- Identifier
- uon:56704
- Rights
- Copyright 2022 Shaun Roy Eslick
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 4 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 682 KB | Adobe Acrobat PDF | View Details Download |