Peters, Vera Berdine Moniek;
(2021)
Fatty acids on the crossroads of immune and metabolic pathways in sepsis.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Background: Sepsis represents life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis comprises various derangements including metabolic, immune and mitochondrial dysfunction and these are likely to be inter-related. The pharmacological impact of nutrition in sepsis is mostly overlooked. Depending on their hydrocarbon chain lengths, degree of unsaturation (number of double bonds between carbon atoms), number, position and orientation of their double bonds, lipids have differential effects on immune function and metabolism to either the potential benefit or detriment the patient. / Objectives: This study examines the literature surrounding nutrition in sepsis, with emphasis on lipids, and the potential therapeutic use of palmitate, butyrate and alpha-linolenic acid in modulating immune function, mitochondrial function and metabolism. / Methods: An in vitro model using human peripheral blood mononuclear cells exposed to lipopolysaccharide (LPS) or clinical strains of bacteria was used to determine the effects of palmitate (long-chain, saturated), butyrate (short-chain, saturated) and alpha-linolenic acid (ALA) (long-chain, unsaturated) on immune and mitochondrial function in sepsis via cytokine secretion, cell-specific flow cytometric analyses and mitochondrial respiration. A rat faecal peritonitis model was then utilised to investigate the impact of intravenous butyrate infusion on metabolism, immune function and mitochondrial function. / Results: Palmitate, butyrate and alpha-linolenic acid had pro-, anti-, and mixed inflammatory effects on cytokine secretion respectively. Butyrate, but not palmitate or alpha-linolenic acid, increased maximal mitochondrial respiration and spare respiratory capacity. Butyrate infusion in vivo stimulated fatty acid metabolism, but did not impact on immune function and may increase mitochondrial stress. / Conclusions: Palmitate and butyrate could potentially impact on sepsis pathology, but at different phases of sepsis. Beneficial in vitro effects of butyrate on immune and mitochondrial function could not be reproduced in vivo. Measuring plasma butyrate levels should be addressed in future studies.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Fatty acids on the crossroads of immune and metabolic pathways in sepsis |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10125495 |
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