Woodcock, Andrea (2023) Characterising the impact of obesity on Dendritic Cell metabolism & function. PhD thesis, National University of Ireland Maynooth.

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Abstract

Obesity is a worldwide epidemic, as of 2016, over 650 million people were living with obesity. Obesity is strongly associated with over 200 comorbidities. In addition, people with obesity (PWO) are more susceptible to infection, and have increased morbidity and mortality following infection, as highlighted during the H1N1 influenza and COVID-19 pandemics. Obesity has also previously been linked to reduced antibody titres following immunisation, depicting dampened vaccine efficacy. Dendritic cells (DCs) play an essential role in activating the adaptive immune response, particularly in stimulating the differentiation of naïve T cells into memory cells. DCs have been shown to be reduced in the periphery of PWO, and this was paired with dysfunctional cytokine production. However, the mechanisms underpinning these alterations remain unclear. Cellular metabolism has been shown to be critical for immune cell function. Therefore, we investigated if obesity impacted DC metabolism using a murine model of obesity. We utilized two different stimulations, bacterial-derived lipopolysaccharide (LPS) and an active virus, Sendai virus (SeV), and demonstrate both can drive robust activation of DCs as measured by cytokine production and metabolic activity. We also map DC metabolism, highlighting glycolysis as a major metabolic pathway and demonstrate metabolic flexibility when exposed to alternative carbon sources, maintaining similar levels of cytokine between glucose, fructose, galactose, or glucose-deprived conditions. We show that DC cytokine production is significantly impacted in our obesity model, especially of IFNβ and IL-6. Finally, we demonstrate reduced cellular metabolism, as measured by protein synthesis in both LPSand SeV-stimulated DCs from mice on the high fat diet. Collectively, our data supports the possibility that defects in DC function are linked to altered cellular metabolism, and this may underpin dysfunc?onal pathogen or vaccine responses.

Item Type:	Thesis (PhD)
Keywords:	Characterising; impact; obesity; Dendritic Cell metabolism; function;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	18341
Depositing User:	IR eTheses
Date Deposited:	02 Apr 2024 10:24
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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